Name: 381-88-4|1,1,1-Trifluoro-2-butanone|95%
Brand: Ambeed
SKU: A910599
Rating: 98 (22 reviews)

1
[ 381-88-4 ]
[ 382-12-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane for 36h; Heating; Irradiation;
32%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 70℃; for 36h; Irradiation with a tungsten lamp;	1.1G A suspension of l,l,l-trifluoro-butan-2-one (10 g, 79.4 mmoles), N- bromosuccinimide (36.7 g, 206.3 mmoles) and benzoyl peroxide (25 mg, 0.1 mmoles) in carbon tetrachloride (100 ml) was irradiated at 70 0C with a tungsten lamp for 36 hours. The suspension was filtered and the filtrate was evaporated in vacuo. The residue was triturated with petrol, filtered and the filtrate was evaporated in vacuo to give 3,3-dibromo-l,l,l-trifluoro-butan-2-one as a pale yellow liquid (13.5 g, 32%) which was a 1:1 mixture of the desired product with residual NBS. The crude product was taken into the next step without purification.
	With bromine; sodium acetate; acetic acid

	With sulfuric acid; bromine; sodium acetate In acetic acid	R.1 REFERENCE EXAMPLE 1 REFERENCE EXAMPLE 1 This is a production example for 3,3-dibromo-1,1,1-trifluoro-2-butanone used in Production Example 13. First, 34.0 g of sodium acetate was dissolved in 270 ml of acetic acid, to which 25 g (0.20 mol) of 1,1,1-trifluoro-2-butanone was added, and while keeping the temperature at 15° to 20° C., 66.3 g (0.42 mol) of bromine was added dropwise over 45 minutes. The reaction mixture was stirred for 5 hours, while keeping the temperature at 15° to 20° C., and then allowed to stand at room temperature for 68 hours. The supernatant was taken and washed with 600 ml of concentrated sulfuric acid. Further washing with 307 ml of concentrated sulfuric acid and distillation under normal pressure gave 28 g (0.10 mol) of 3,3-dibromo-1,1,1-trifluoro-2-butanone. STR56
	With bromine; sodium acetate; acetic acid at 15 - 20℃; for 73.75h;	1 Reference Example 1 Reference Example 1 This is a production example for 3,3-dibromo-1,1,1-trifluoro-2-butanone used in Production Example 13. First, 34.0 g of sodium acetate was dissolved in 270 ml of acetic acid, to which 25 g (0.20 mol) of 1,1,1-trifluoro-2-butanone was added, and while keeping the temperature at 15° to 20° C., 66.3 g (0.42 mol) of bromine was added dropwise over 45 minutes.. The reaction mixture was stirred for 5 hours, while keeping the temperature at 15° to 20° C., and then allowed to stand at room temperature for 68 hours.. The supernatant was taken and washed with 600 ml of concentrated sulfuric acid.. Further washing with 307 ml of concentrated sulfuric acid and distillation under normal pressure gave 28 g (0.10 mol) of 3,3-dibromo-1,1,1-trifluoro-2-butanone. .

Reference： [1]Cushman, Mark; Patel, Hemantkumar H.; Scheuring, Johannes; Bacher, Adelbert [Journal of Organic Chemistry, 1992, vol. 57, # 21, p. 5630 - 5643]
[2]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - WO2006/70202, 2006, A1 Location in patent: Page/Page column 83
[3]Belcher et al. [Journal of the Chemical Society, 1957, p. 2393,2395]
[4]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - US6090753, 2000, A
[5]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - US6348628, 2002, B1 Location in patent: Page column 55-56

2
[ 381-88-4 ]
[ 382-01-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; bromine

Reference： [1]Rausch et al. [Journal of Organic Chemistry, 1956, vol. 21, p. 1328] McBee et al. [Journal of the American Chemical Society, 1956, vol. 78, p. 4053,4056] Belcher et al. [Journal of the Chemical Society, 1957, p. 2393,2395]

3
[ 344-00-3 ]
[ 381-88-4 ]

Yield	Reaction Conditions	Operation in experiment
95.2%	With methanesulfonic acid; trifluoroacetic acid at 120℃; for 3h;	1 Example 1 In 500mL equipped with distillation column,Magnetic stirrer and thermometer in a glass reactor were charged with 0.6 mol of anhydrous methanesulfonic acid,Start stirring,At an internal temperature of 120 ° C,1.0 mol was added dropwise ethyl 2-methyl-4,4,4-trifluoroacetoacetate and 1.0 mol of trifluoroacetic acid,Dropping time for 3h,The product 1,1,1-trifluoro-2-butanone was recovered at a reflux ratio of 1: 1And ethyl trifluoroacetate. To obtain 120 g of 1,1,1-trifluoro-2-butanone in an amount of 99.2%The yield was 95.2%.To obtain 132 g of ethyl acetate trifluoroacetate in an amount of 99.9%The yield was 93.0%.
	With sulfuric acid; acetic acid
	(i) Na, Et₂O, (ii) aq. H₂SO₄; Multistep reaction;

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD - CN106365972, 2017, A Location in patent: Paragraph 0021; 0022
[2]McBee et al. [Journal of the American Chemical Society, 1956, vol. 78, p. 4053,4056]
[3]Burdon,J.; McLoughlin,V.C.R. [Tetrahedron, 1964, vol. 20, p. 2162 - 2166]

4
[ 381-88-4 ]
[ 431-36-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With formic acid; tetrabutylammomium bromide; water; potassium formate at 30℃; for 21h; Inert atmosphere; Autoclave;	36 Example 36 Under argon gas atmosphere, a ruthenium complex RuCl[(S,S)-Tsdpen](mesitylene) (61.1 mg, 0.10 mmol), potassium formate (5.1 g, 60.9 mmol), tetrabutylammonium bromide (TBAB) (0.47 g, 1.5 mmol), water (6.0 mL), formic acid (0.11 mL, 2.9 mmol; 0.1 equivalent relative to the ketone used) and 1,1,1-trifluoro-2-butanone (4.0 mL, 29 mmol, substrate/catalyst ratio: 300) were introduced in a 100-mL glass autoclave. The container was sealed and stirred at 30°C for 21 h. After the reaction was complete, the reaction solution was collected with dimethyl sulfoxide (DMSO), and GC was measured by adding N,N-dimethylformamide (1.0 mL, 12.9 mmol) as the internal standard material. The conversion obtained from the amount of remaining ketone substrate was 100%. Optical purity was 96.4%ee. We confirmed that the reaction can proceed well with 1,1,1-trifluoro-2-butanone as well.
28%	With sodium tetrahydroborate In diethyl ether; water at 0 - 32℃; for 16h;	11 A41: l,l,l-trifluorobutan-2-ol To a solution of l,l,l-trifluorobutan-2-one (30 g, 237.94 mmol) in ether (300 mL) and water (10 mL) was added a solution of NaBLL (9.0 g, 237.94 mmol) in water (40 mL) in portions at 0 °C. The mixture was stirred at 32 °C for 16 hours. 0.5 M HC1 was added to acidify to pH 6. The aqueous layer was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over anhydrous NaiSCL, filtered and concentrated under reduced pressure. The crude product was distilled under reduced pressure (water pump, bp 75~80°C) to afford the product (12 g, 67.45 mmol, 28% yield) as an oil. *H NMR (400 MHz, CDCh) dH = 3.90-3.78 (m, 1H), 2.80-2.60 (m, 1H), 1.83-1.70 (m, 1H), 1.60-1.55 (m, 1H), 1.07 (t, 3H).
	With lithium aluminium tetrahydride In diethyl ether

With sodium tetrahydroborate In water Ambient temperature; Yield given;

Reference： [1]Current Patent Assignee: KANTO KAGAKU HOLDINGS K.K. - EP2399895, 2011, A2 Location in patent: Page/Page column 14
[2]Current Patent Assignee: PRAXIS PRECISION MEDICINES INC - WO2021/108513, 2021, A1 Location in patent: Page/Page column 59
[3]Gassen, Karl-Rudolf; Kirmse, Wolfgang [Chemische Berichte, 1986, vol. 119, # 7, p. 2233 - 2248]
[4]Xiao, Ling; Yamazaki, Takashi; Kitazume, Tomoya; Yonezawa, Tetsuo; Sakamoto, Yoshitake; Nogawa, Kouji [Journal of Fluorine Chemistry, 1997, vol. 84, # 1, p. 19 - 23]

5
[ 381-88-4 ]
[ 101054-89-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide; hydroxylamine hydrochloride In water for 4h; Heating;
	With hydroxylamine hydrochloride; sodium acetate In water at -5 - 20℃; Large scale;	General procedure General procedure: Hydroxylamine hydrochloride (3.7 Kg, 53 mol) was added toa solution of sodium acetate (5.3 Kg, 64 mol) in 20 L water. Subsequently, 1,1,1-trifluoroacetone (3 Kg, 26.8 mol) was dosed within 0.5 h at a temperature range of -5 to + 10 °C. The reaction mixture was stirred at room temperature overnight.The crude oxime was diluted with a solution of sodium carbonate (0.7 Kg) in 5 L water and then separated. The low-boiling-point substances were then removed under reduced pressureto yield a pale yellow solid which was used for the next step without further purification.

Reference： [1]Gassen, Karl-Rudolf; Kirmse, Wolfgang [Chemische Berichte, 1986, vol. 119, # 7, p. 2233 - 2248]
[2]Jiang; Cheng; Yuan [Asian Journal of Chemistry, 2015, vol. 27, # 7, p. 2406 - 2408]

6
[ 74-84-0 ]
[ 407-25-0 ]
[ 381-88-4 ]
[ 64-19-7 ]
[ 802294-64-0 ]
[ 68267-65-2 ]

Yield	Reaction Conditions	Operation in experiment
0.68 mmol	With ethene; dihydrogen peroxide In water at 75 - 80℃; for 24h; Further byproducts given;

Reference： [1]Hogan, Terrence; Sen, Ayusman [Journal of the American Chemical Society, 1997, vol. 119, # 11, p. 2642 - 2646]

7
[ 74-84-0 ]
[ 407-25-0 ]
[ 381-88-4 ]
[ 383-63-1 ]
[ 802294-64-0 ]
[ 68267-65-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 0.80 mmol 2: 0.15 mmol	With tetraethyllead(IV) at 90℃; for 24h; Further byproducts given;
1: 0.33 mmol 2: 0.68 mmol	With ethene; dihydrogen peroxide In water at 90℃; for 24h; Further byproducts given;

Reference： [1]Hogan, Terrence; Sen, Ayusman [Journal of the American Chemical Society, 1997, vol. 119, # 11, p. 2642 - 2646]
[2]Hogan, Terrence; Sen, Ayusman [Journal of the American Chemical Society, 1997, vol. 119, # 11, p. 2642 - 2646]

8
[ 381-88-4 ]
[ 1099-45-2 ]
Z-3-trifluoromethylpent-2-enoic acid ethyl ester [ No CAS ]
E-3-trifluoromethylpent-2-enoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether at 50 - 60℃; for 24h; Title compound not separated from byproducts;

Reference： [1]Wang, Pin; Tang, Yi; Tirrell, David A. [Journal of the American Chemical Society, 2003, vol. 125, # 23, p. 6900 - 6906]

9
[ 381-88-4 ]
[ 2999-46-4 ]
ethyl (Z)-3-ethyl-4,4,4-trifluoro-2-formylamino-2-butenoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: Ethyl isocyanoacetate With potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78 - 20℃;

Reference： [1]Enders, Dieter; Chen, Zai-Xin; Raabe, Gerhard [Synthesis, 2005, # 2, p. 306 - 310]

10
[ 381-88-4 ]
[ 196929-78-9 ]
2-Methyl-propane-2-sulfinic acid [1-trifluoromethyl-prop-(E)-ylidene]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61 % Spectr.	With titanium(IV) isopropylate In hexane at 20℃; for 3h;

Reference： [1]Wang, Hua; Zhao, Xiaoming; Li, Youhua; Lu, Long [Organic Letters, 2006, vol. 8, # 7, p. 1379 - 1381]

11
[ 381-88-4 ]
[ 118-92-3 ]
1,2-dihydro-2-ethyl-2-(trifluoromethyl)-4H-3,1-benzoxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With gallium(III) triflate In dichloromethane at 100℃; for 7h;

Reference： [1]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]

12
[ 381-88-4 ]
[ 496-72-0 ]
2-ethyl-5-methyl-2-(trifluoromethyl)benzimidazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With phosphotungstic acid In toluene at 50℃; for 5h; Inert atmosphere; Sealed tube;
89%	With gallium(III) triflate In dichloromethane at 50℃; for 5h;

Reference： [1]Feng, Xue; Yang, Tao; He, Xing; Yu, Bing; Hu, Chang-Wen [Applied Organometallic Chemistry, 2018, vol. 32, # 5]
[2]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]

13
[ 381-88-4 ]
[ 95-83-0 ]
5-chloro-2-ethyl-2-(trifluoromethyl)benzimidazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With Nafion-H In dichloromethane at 120℃; for 6h;
80%	With gallium(III) triflate In dichloromethane at 50℃; for 5h;

Reference： [1]Prakash, G. K. Surya; Vaghoo, Habiba; Panja, Chiradeep; Molnar, Arpad; Mathew, Thomas; Olah, George A. [Synthesis, 2008, # 6, p. 897 - 902]
[2]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]

14
[ 381-88-4 ]
[ 95-54-5 ]
2-ethyl-2-(trifluoromethyl)benzimidazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With Nafion-H In dichloromethane at 120℃; for 4h;
87%	With phosphotungstic acid In toluene at 50℃; for 5h; Inert atmosphere; Sealed tube;
83%	With gallium(III) triflate In dichloromethane at 50℃; for 5h;

Reference： [1]Prakash, G. K. Surya; Vaghoo, Habiba; Panja, Chiradeep; Molnar, Arpad; Mathew, Thomas; Olah, George A. [Synthesis, 2008, # 6, p. 897 - 902]
[2]Feng, Xue; Yang, Tao; He, Xing; Yu, Bing; Hu, Chang-Wen [Applied Organometallic Chemistry, 2018, vol. 32, # 5]
[3]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]

15
[ 381-88-4 ]
[ 95-55-6 ]
2-ethyl-2-(trifluoromethyl)benzoxazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With Nafion-H In dichloromethane at 120℃; for 5h;
60%	With gallium(III) triflate In dichloromethane at 75℃; for 4h;

Reference： [1]Prakash, G. K. Surya; Vaghoo, Habiba; Panja, Chiradeep; Molnar, Arpad; Mathew, Thomas; Olah, George A. [Synthesis, 2008, # 6, p. 897 - 902]
[2]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]

16
[ 381-88-4 ]
[ 137-07-5 ]
2-ethyl-2-(trifluoromethyl)benzothiazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With gallium(III) triflate In dichloromethane at 50℃; for 4h;
73%	With Nafion-H In dichloromethane at 120℃; for 20h;

Reference： [1]Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Vaghoo, Habiba; Venkataraman, Karthik; Olah, George A. [Organic Letters, 2007, vol. 9, # 2, p. 179 - 182]
[2]Prakash, G. K. Surya; Vaghoo, Habiba; Panja, Chiradeep; Molnar, Arpad; Mathew, Thomas; Olah, George A. [Synthesis, 2008, # 6, p. 897 - 902]

17
[ 75-52-5 ]
[ 381-88-4 ]
(2S)-1,1,1-trifluoro-2-(nitromethyl)butan-2-ol [ No CAS ]
(2R)-1,1,1-trifluoro-2-(nitromethyl)butan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In acetonitrile at -40℃; for 96h; Title compound not separated from byproducts.;
	With (ΔS,S,S)-[Binolam₃La(OTf)₃]; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In acetonitrile at -40℃; for 96h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
18 % ee	With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,2'R)-(Z)-(Sa,Sa)-6'-((4-(dimethylamino)pyridin-2-yl)amino)-2,2',4,4',7,7'-hexamethyl-2,2',3,3'-tetrahydro-[1,1'-biindenylidene]-6-yl)thiourea In toluene at -25℃; Overall yield = 70 %;

54 % ee	With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,2'R)-6'-((4-(dimethylamino)pyridin-2-yl)amino)-2,2',4,4',7,7'-hexamethyl-2,2',3,3'-tetrahydro-[1,1'-biindenylidene]-6-yl)thiourea In toluene at -25℃; Overall yield = 72 %;
90 % ee	With (R)-1-(1,1-bis(3,5-di-tert-butylphenyl)-3-(dimethylamino)-1-methoxypropan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)urea In 2-methyltetrahydrofuran at -20℃; for 48h; Overall yield = 91 percent; enantioselective reaction;	3. General Procedure for the Enantioselective Henry Reaction and characterization data for products 2 General procedure: A mixture of α-trifluoromethyl ketones 1 (0.2 mmol, 1.0 equiv.), catalyst 4l (0.01 mmol, 5 mol%) and nitroalkanes (2.0 mmol, 10.0 equiv.) were dissolved in 2-Me-THF (1.0 mL). The resulting mixture was stirred for 48 h at -20 °C until the reaction finished (monitored by TLC). The crude products were purified by flash column chromatography on silica gel (VPE / VEA = 6 : 1) to yield pure products 2a-2q. The enantiomeric excess of the product was determined by chiral HPLC.

Reference： [1]Tur, Fernando; Saa, Jose M. [Organic Letters, 2007, vol. 9, # 24, p. 5079 - 5082]
[2]Location in patent: experimental part Tur, Fernando; Mansilla, Javier; Lillo, Victor J.; Saa, Jose M. [Synthesis, 2010, # 11, p. 1909 - 1923]
[3]Vlatkovic, Matea; Bernardi, Luca; Otten, Edwin; Feringa, Ben L. [Chemical Communications, 2014, vol. 50, # 58, p. 7773 - 7775]
[4]Vlatkovic, Matea; Bernardi, Luca; Otten, Edwin; Feringa, Ben L. [Chemical Communications, 2014, vol. 50, # 58, p. 7773 - 7775]
[5]Meng, Xiangyu; Luo, Yueyang; Zhao, Gang [Tetrahedron Letters, 2020, vol. 61, # 45]

18
[ 75-52-5 ]
[ 381-88-4 ]
1,1,1-trifluoro-2-(nitromethyl)butan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	at 80℃; for 2h; Microwave irradiation;
	With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 20℃;
	With potassium carbonate In dichloromethane at 20 - 30℃;	General procedure: To a solution of the trifluoromethyl ketone (14.4 mmol) in MeNO2 (14.4 mmol) was added granularpotassium carbonate 2g in CH2Cl2 (60 mL). The mixture was stirred for overnight at 20-30. After thereaction was completed, water (20 mL) was added, successively with 1N HCl to adjust pH to 5-6. Theorganic phase was separated and the aqueous phase was extracted with CH2Cl2 (20 mL * 2). Thecombined organic phase was washed with water (20 mL) then dried (Na2SO4). Removal of the solventunder reduced pressure gave an oily residue of the corresponding crude nitroalcohol, which was usedwithout further purification.

With triethylamine at 25℃; for 12h;

Reference： [1]Colombo Dugoni, Greta; Mele, Andrea; Sacchetti, Alessandro [Organic and Biomolecular Chemistry, 2020, vol. 18, # 41, p. 8395 - 8401]
[2]Tur, Fernando; Saa, Jose M. [Organic Letters, 2007, vol. 9, # 24, p. 5079 - 5082]
[3]Lai, Xiaoyan; Zha, Gaofeng; Liu, Wei; Xu, Yan; Sun, Panpan; Xia, Tao; Shen, Yongcun [Synlett, 2016, vol. 27, # 13, p. 1983 - 1988]
[4]Otevrel, Jan; Svestka, David; Bobal, Pavel [Organic and Biomolecular Chemistry, 2019, vol. 17, # 21, p. 5244 - 5248]

19
aqueous sulphuric acid [ No CAS ]
[ 381-88-4 ]
[ 7664-93-9 ]
[ 107-92-6 ]
[ 72114-82-0 ]

Yield	Reaction Conditions	Operation in experiment
	In water	6 EXAMPLE 6 The butyric acid used as starting material may be obtained as follows: 1,1,1,-Trifluorobutan-2-one (14 g.) is added dropwise to a stirred solution of potassium cyanide (8.2 g.) in water (30 ml.) which is maintained at 0° C. 25% V/v aqueous sulphuric acid (50 ml.) is added and the mixture is stirred at laboratory temperature for 16 hours and is then extracted with ether. The extract is washed with water, dried and evaporated to dryness and the residual oil is added dropwise to concentrated sulphuric acid (6 ml.) which is maintained at 70°-75° C. Water (50 ml.) is added and the mixture is heated at 95°-100° C. for 72 hours, cooled and extracted with ether. The ethereal extract is washed with water and then extracted with saturated aqueous sodium bicarbonate solution. The extract is acidified with equeous hydrochloric acid and then extracted with ether. The ethereal extract is washed with water, dried and evaporated to dryness and the residue is crystallized from a mixture of chloroform and petroleum ether (b.p. 60°-80° C.). There is thus obtained 2-hydroxy-2-trifluoromethylbutyric acid, m.p. 95°-100° C.

Reference： [1]Current Patent Assignee: AKZO NOBEL NV - US4191775, 1980, A

20
[ 381-88-4 ]
[ 1066-54-2 ]
[ 1044277-02-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78℃; for 4h; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane	1.1 Step 1: 3-(trifluoromethyl)-1-(trimethylsilyl)pent-1-yn-3-ol Step 1: 3-(trifluoromethyl)-1-(trimethylsilyl)pent-1-yn-3-ol To a solution of trimethylsilylacetylene (6.0 g, 61.1 mmol) in THF (80 mL) cooled at -78° C., a 1.6M n-butyllithium in hexanes (38 mL, 61.1 mmol) was added dropwise. The solution was then stirred 1 hour, before a solution trifluoromethylethylketone (10 g, 79.4 mmol) in 25 mL of THF was added slowly. The reaction was stirred at -78° C. for 4 hours. The reaction was then poured into a saturated ammonium chloride solution and the aqueous layer was extracted (4*) with diethyl ether. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue obtained was used as such for the next step. 1H NMR (400 MHz, acetone-d6): 5.83 (s, 1H), 1.80 (q, 2H), 1.14 (t, 3H), 0.18 (s, 9H).
	Stage #1: trimethylsilylacetylene With n-butyllithium In tert-butyl methyl ether at -67 - -50℃; for 1.75h; Stage #2: 1,1,1-trifluoro-2-butanone In tert-butyl methyl ether at -50℃; for 1.33333h;	1.A.1 EXAMPLE 1A Alternate Method for the Preparation of (S)-4-(3-fluorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-2H-chromen-2-one Step 1. Alternate Method for the Preparation of (5)-4-(3-fluorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-2H-chromen-2-one A 100 mL flask equipped with a mechanical stirrer, a thermocouple, a nitrogen inlet and a cooling bath was charged with trimethylsilyl acetylene (3.5 g, 1.50 eq) and MTBE (12.0 mL). The mixture was cooled to -67° C. and 2.26 M n-BuLi (11.2 mL, 1.05 eq) was added to the solution over 1 hr, keeping the reaction mixture below -50° C. The reaction mixture was aged 45 min before the addition of 1,1,1-trifluoro-2-butanone (3.3 mL, 1.00 eq) over a period of 1 hr (internal temperature was kept below -50° C.). The mixture was aged 20 min, then p-nitrobenzoyl chloride (4.7 g, 1.05 eq) was added over 1 hr as a THF solution (7.0 mL), keeping the reaction mixture below -30° C. The reaction mixture was allowed to warm to 5° C. over 3 hrs. The reaction was quenched by careful addition of water (9.0 mL). To the reaction mixture was added Solka Floc (0.25 g, 8% wt) and the mixture was stirred 20 min. The biphasic mixture was filtered over Solka Floc, then transferred to a separatory funnel where the layers were separated. The organic layer was washed with 1/2 saturated solution of NaHCO3 (2*15.0 mL) and with brine (15.0 mL) to provide 1-ethyl-1-trifluoromethyl-3-trimethylsilylprop-2-yn-1-yl 4-nitrobenzoate (TMS-acetylene ester).
	Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone at -78 - 20℃; for 2h;	1.4 Step 4: 3-(trifluoromethyl)pent-l-yn-3-ol; To a mixture of tϖmethylsilylacetylene (19.4 g, 198 mmol, 1 eq) in THF (500 mL, 0.396M) stirred at - 78°C under an atmosphere of nitrogen, n-butyllithium 1.6M hexanes (124 mL, 198 mmol, 1 eq) was added. The resulting mixture was stirred at -78°C forl h. Then 1 , 1 , 1 -trifluoro-2-butanone (25.0 g, 198 mmol, 1 eq) was added dropwise at -78°C and the resulting mixture was stirred at rt for 2 h. The reaction was quenched by the addition of a saturated NaHCO3 solution at 0 0C . The organic layer was separated and the aqueous phase was extracted with ether/hexane (1 : 1). The organic layers were combined, washed with brme, dried over Na2SO4. The solvent was removed by careful distillation. The crude thus obtained was re-dissolved in THF (200 mL, 1 M) under atmosphere of nitrogen at 00C, tetrabutylammonium fluoride IM THF (238 mL, 238 mmol, 1 2 eq) was added dropwise. The resulting mixture was stirred at rt for 2 h. The reaction was quenched by the addition of brme. The organic layer was separated and the aqueous phase was extracted with hexane. The organic layers were combined, washed with brme, dried over Na2SO4. The solvent was removed by careful distillation and residue was purified by distillation (collect the fraction between 100-140 0C) to afford the titled compound. 1H NMR δ (ppm)( Acetone): 5.86 (1 H, s), 3.27 (1 H, s), 1.91-1 81 (2 H, m), 1.15 (3 H, t).

	Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78 - 20℃;
	With n-butyllithium In tetrahydrofuran; hexane at -78℃;	1.9 To (trimethylsilyl)acetylene (2.45 g, 25 mmol) in THF (100 mL) at -78 °C was added n- butyllithium (1.6 M in hexanes, 19 mL, 30 mmol) dropwise. After stirring for 1 hour at -78 °C, 1, 1,1- trifluoro-2-butanone (4 mL, 30 mmol) in THF (10 mL) was added dropwise, and the reaction was slowly warmed to room temperature. The mixture was diluted with Et20 (300 mL) and washed with H20, and then dried, filtered, and concentrated give the title compound.
	Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78 - 20℃;	1.7 Step 7: 3-Trifluoromethyl-l-trimethylsilanyl-pent-l-yn-3-ol[00339] To (trimethylsilyl)acetylene (2.45 g, 25 mmol) in THF (100 mL) at -78°C was added n- butyllithium (1.6 M in hexanes, 19 mL, 30 mmol) dropwise. After stirring for 1 hour at -78°C, 1,1, 1- trifluoro-2-butanone (4 mL, 30 mmol) in THF (10 mL) was added dropwise, and the reaction was slowly allowed to warm to room temperature. The mixture was diluted with Et20 (300 mL) and washed with H20, then dried, filtered, and concentrated to give the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2008/188521, 2008, A1 Location in patent: Page/Page column 13; 17
[2]Current Patent Assignee: MERCK & CO INC - US2008/188521, 2008, A1 Location in patent: Page/Page column 19
[3]Current Patent Assignee: MERCK & CO INC - WO2007/16784, 2007, A1 Location in patent: Page/Page column 31; 43
[4]Location in patent: scheme or table Li, Lianhai; Berthelette, Carl; Chateauneuf, Anne; Ouellet, Marc; Sturino, Claudio F.; Wang, Zhaoyin [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7440 - 7443]
[5]Current Patent Assignee: PANMIRA PHARMACEUTICALS, INC. - WO2011/38086, 2011, A2 Location in patent: Page/Page column 88
[6]Current Patent Assignee: PANMIRA PHARMACEUTICALS, INC. - WO2011/38097, 2011, A2 Location in patent: Page/Page column 75

21
[ 381-88-4 ]
1-propynylmagnesium bromide [ No CAS ]
[ 1044277-57-7 ]

Yield	Reaction Conditions	Operation in experiment
50 %Spectr.	In tetrahydrofuran at 20℃; for 1h;	27.1 Step 1: 3-(trifluoromethyl)hex-4-yn-3-ol Step 1: 3-(trifluoromethyl)hex-4-yn-3-ol To ethyl trifluoromethyl ketone (5.00 g, 40.0 mmol) in THF (20 ml) at room temperature was added 1-propynyl magnesium bromide (0.5 M in THF, 60 mL, 30.0 mmol). The reaction mixture was allowed to stand at rt 1 h, and concentrated in vacuo. The residue was partitioned between Et2O and aq. NH4OAc, the phases were separated, and the organic phase washed with brine, dried over MgSO4, filtered and concentrated (not to complete dryness), to afford a 50 wt. % solution (estimated by 1H NMR) of the title compound (remainder THF and Et2O), which was used without further purification. 1H NMR (400 MHz, DMSO-d6): 6.63 (s, 1H), 1.87 (s, 3H), 1.75-1.63 (m, 2H), 1.04 (t, 3H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2008/188521, 2008, A1 Location in patent: Page/Page column 27

22
[ 383-63-1 ]
[ 925-90-6 ]
[ 381-88-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl trifluoroacetate,; ethylmagnesium bromide In diethyl ether at -78℃; for 1h; Stage #2: With hydrogenchloride In diethyl ether; water	4.1 Step 1:To a solution of ethyl magnesium bromide in diethyl ether prepared from 18.4 g of bromoethane, 4.3 g of magnesium and 150 ml of diethyl ether was added dropwise 20 g of ethyl trifluoroacetate under cooling at -78°C. The mixture was stirred at the same temperature for 1 hour, and then warmed to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate and then filtered to obtain a solution of 1, 1, l-trifluoro-2-butanone in diethyl ether.

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2008/143332, 2008, A1 Location in patent: Page/Page column 141

23
[ 867-13-0 ]
[ 381-88-4 ]
[ 558452-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at 0℃; for 1h;	4.2 Step 2: To a suspension of 5.6 g of sodium hydride (60% in oil) in 500 ml of tetrahydrofuran was added dropwise 31.6 g of ethyl diethylphosphonoacetate under ice-cooling. After the mixture was stirred at the same temperature for 10 minutes, the a solution of 1, 1, 1-trifluoro-2-butanone in diethyl ether obtained in Step 1 was added dropwise thereto, The mixture was stirred at the same temperature for 1 hour, and then warmed to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain crude ethyl 3- trifluoromethyl-2-pentenoate .

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2008/143332, 2008, A1 Location in patent: Page/Page column 141-142

24
[ 381-88-4 ]
C₁₄H₁₅ClF₃N₃O [ No CAS ]
[ 917891-86-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In ethanol; water at 80℃; for 18h;	126 Example 126 9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one; Compound 229, Structure 12 of Scheme II, where RA=chloro, R1=methyl, R3=trifluoromethyl, R5=2,2,2-trifluoroethylTo a mixture of compound 7 (RA=chloro, RB=2-propyl) in trifluoroacetic acid at 0° C. was added trifluoroacetaldehyde ethyl hemiacetal, followed by NaBH4. After 2.5 hrs the reaction mixture was poured into ice/water. Solid was filtered and washed with water, then dried. Compound 8 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was obtained as a yellow solid. To a mixture of compound 8 and sodium nitrite in DMF at 0° C. was added slowly 2N HCl. After 30 min., water was added. Solid was filtered and washed with water. Compound 9 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was obtained as a white solid. To a mixture of compound 9 in dry THF at 0° C. was added slowly lithium aluminumhydride (1.0 M in THF). That reaction mixture was then stirred at room temperature for 1 hour. EtOAc was added slowly at 0° C. The mixture was filtered through celite. After removal of solvent, crude compound 10 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was used directly in the next step without further purification.Compound 10, 1,1,1-trifluoro-2-butanone, EtOH and conc. HCl were heated at 80° C. in a sealed tube for 18 hrs. The mixture was then poured into water. Solid was filtered and purified by chromatography. Compound 229 was obtained as a white solid. 1H NMR (500 MHz, acetone-d6) 11.13 (s, 1H), 8.08 (d, J=9.1 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 6.78 (s, 1H), 5.35 (q, J=8.5 Hz, 2H), 2.70 (q, J=2.6 Hz, 2H).

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US2009/30027, 2009, A1 Location in patent: Page/Page column 62

25
[ 381-88-4 ]
[ 18106-71-3 ]
[ 1123496-04-7 ]

Yield	Reaction Conditions	Operation in experiment
41%	With copper(II) bis(trifluoromethanesulfonate) In N,N-dimethyl-formamide at 50℃;

Reference： [1]Demir, Ayhan S.; Esiringue, Lker; Goellue, Mehmet; Reis, Oemer [Journal of Organic Chemistry, 2009, vol. 74, # 5, p. 2197 - 2199]

26
[ 75-52-5 ]
[ 381-88-4 ]
(2R)-1,1,1-trifluoro-2-(nitromethyl)butan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With (R)-(5-(3-(3,5-bis-(trifluoromethyl)phenyl)ureido)-6-methoxyquinolin-4-yl)(8-ethylquinuclidin-2-yl)methyl 3,5-bis-(trifluoromethyl)phenylcarbamate In tert-butyl methyl ether at -30℃; for 72h; Inert atmosphere; optical yield given as %ee;
67%	With (1R)-(6-hydroxyquinolin-4-yl)(8-vinylquinuclidin-2-yl)methyl 3,5-di(trifluoromethyl)benzoate In dichloromethane at -78 - -25℃; optical yield given as %ee; enantioselective reaction;

Reference： [1]Palacio, Carole; Connon, Stephen J. [Organic Letters, 2011, vol. 13, # 6, p. 1298 - 1301]
[2]Location in patent: scheme or table Bandini, Marco; Sinisi, Riccardo; Umani-Ronchi, Achille [Chemical Communications, 2008, # 36, p. 4360 - 4362]

27
[ 109-97-7 ]
[ 381-88-4 ]
C₈H₁₀F₃NO [ No CAS ]
[ 1096376-01-0 ]

Yield	Reaction Conditions	Operation in experiment
	With zirconium(IV) tert-butoxide; (R)-3,3'-dibromo-1,1'-bi-2-naphthol In benzene at 20℃; for 1.2h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;

Reference： [1]Blay, Gonzalo; Fernandez, Isabel; Monleon, Alicia; Pedro, Jose R.; Vila, Carlos [Organic Letters, 2009, vol. 11, # 2, p. 441 - 444]

28
[ 381-88-4 ]
[ 1099-45-2 ]
[ 558452-22-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	In diethyl ether at 0 - 20℃;	1B Example 1B A solution of 70.0 g (201 mmol) carbethoxymethylene triphenylphosphorane in 300 mL diethyl ether was cooled to 0° C. and 25.0 g (198 mmol) 1,1,1-trifluorobutanone were added. The solution was warmed to room temperature and stirred over night. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by vacuum distillation (170 mbar and 130° C. bath temperature, main fraction: 95-96° C.). 29.0 g (75%) of the product were obtained as an oil.HPLC-MS (M1): Rt=1.77 minMS (ESI pos): m/z=196 (M+H)+
75%	In diethyl ether at 0 - 20℃;	1A A solution of 70 g (201 mmol) carbethoxymethylene triphenylphosphorane in 300 ml_ diethyl ether was cooled to 00C and 25 g (198 mmol) 1.,1 ,1 -thfluorobutanone was added. The solution was warmed to room temperature and stirred over night. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure (700 mbar and 400C bath temperature). The residue was purified by vacuum distillation (170 mbar and 1300C bath temperature, main fraction: 95-96°C). 29 g (75 %) of the product were obtained as colourless oil.HPLC-MS (Method 1 ): Rt: 1.77 min. + MS (ESI pos): m/z = 196 (M+H)4
	In dichloromethane at 0℃; for 0.25h;	F.1 [00191] Step 1 : A solution of ethyl 2-(triphenylphosphoranylidene)acetate (15 g, 44 mmol) in dichloromethane (26 mL, 40 mmol) was cooled to 0 °C and treated with 1,1,1- trifluorobutan-2-one (5 g, 40 mmol). The mixture was stirred at 0 °C for 15 minutes. The reaction mixture was concentrated in vacuo (water bath below 10 °C and vacuum at 170 Torr). With concentration Ph3PO started to precipitate out. The solids were filtered off washing with Et20. The filtrate collected was treated with Et20 (20 mL), and the solids formed were decanted off. The liquid isolated was subjected to fractional distillation (oil bath at 45-50 °C vacuum at 300 Torr) to provide a mixture of E and Z isomers of ethyl 3- (trifluoromethyl)pent-2-enoate. lH NMR (400 MHz, CDC13) δ 6.269 (s, 1H), 4.23 (q, J=7.027 Hz, 2H), 2.72-2.663 (m, 2H), 1.317 (t, J=7.027, 3H), 1.208 (t, J=7.027 Hz, 3H).

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2012/115863, 2012, A1 Location in patent: Page/Page column 38
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2009/121919, 2009, A1 Location in patent: Page/Page column 149
[3]Current Patent Assignee: PFIZER INC; ROCHE HOLDING AG - WO2015/103137, 2015, A1 Location in patent: Paragraph 00191

29
[ 381-88-4 ]
[ 5685-05-2 ]
[ 808140-82-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.25h; Stage #2: 2-mercaptothiazole In tetrahydrofuran for 0.0833333h; Stage #3: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 3h;	1.2 Step 2: l.l.l-trifluoro-2-(2-mercapto-L3-thiazol-5-vDbutan-2-ol To a solution of diisopropylamine (4.32g, 42.6 mmol) in 50 ml of THF at -78 °C wasadded BuLi (1.6 M in hexanes, 26.6 ml, 42.6 mmol). After 15 min, a solution of 2-mercaptothiazole (2.0g, 17.0 mmol) in 10 ml of THF was added dropwise. After 5 min, l,l,l-trifluoro-2-butanone (1.07 g, 8.5mmol) was added. The mixture was stirred 3 h at -78 °C and partitioned between aqueous NHiCl andEtOAc. The layers were separated and the aqueous phase was extracted with EtOAc. The combinedorganic layers were dried over anhydrous MgSO4. The solvent was evaporated and the residuechromatographed on silica gel (hexanes: EtOAc; 1:1) to give the title compound.
	With lithium diisopropyl amide In tetrahydrofuran at -78℃;
	Stage #1: 2-mercaptothiazole With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.166667h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 6h; Stage #3: With water; ammonium chloride In tetrahydrofuran at 20℃;	10.A.1 Step 1: 1,1,1-Trifluoro-2-(2-mercapto-thiazol-5-yl)-butan-2-ol (10b) iPr2NH (2.0 g, 19.9 mmol) was dissolved in THF (23 mL) and cooled to -78° C. n-Butyllithium (2.5M, 8.0 mL, 19.9 mmol) was added dropwise, followed by thiazole-2-thiol (0.9 g, 7.9 mmol) in THF (5 mL). After 10 minutes, trifluoro-2-butanone (0.5 g, 4.0 mmol) was added and the reaction was stirred at -78° C. for 6 hours. The reaction was warmed to room temperature and quenched with 5% aqueous NH4Cl (20 mL). The aqueous layer was acidified and extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (50% EtOAc in hexanes) to give the desired product, 10b.

Stage #1: 2-mercaptothiazole With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.583333h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 6h;

15.1 Diisopropylamine (2.01 g, 19.9 mmol) was dissolved in THF (23 mL) and cooled to -78 °C. n-Butyllithium (2.5 M in THF, 7.96 mL, 19.9 mmol) was slowly added and the reaction stirred for 15 minutes. 2-Mercaptothiazole (0.948 g, 7.93 mmol) in THF (5 mL) was added over 10 minutes. After stirring for 10 minutes, 1 , 1 , 1 -trifluoro-butan-2-one (0.5 g, 3.97 mmol) was added. After stirring at -78 °C for 6 hours, the reaction was allowed to warm to room temperature and submitted to standard aqueous workup. The residue was purified via silica gel chromatography (0-50% EtOAc in hexanes) to yield the title compound.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/108720, 2004, A1 Location in patent: Page 38
[2]Location in patent: scheme or table Ducharme, Yves; Blouin, Marc; Brideau, Christine; Chateauneuf, Anne; Gareau, Yves; Grimm, Erich L.; Juteau, Helene; Laliberte, Sebastien; MacKay, Bruce; Masse, Frederic; Ouellet, Marc; Salem, Myriam; Styhler, Angela; Friesen, Richard W. [ACS Medicinal Chemistry Letters, 2010, vol. 1, # 4, p. 170 - 174]
[3]Current Patent Assignee: PANMIRA PHARMACEUTICALS, INC. - US2007/173508, 2007, A1 Location in patent: Page/Page column 114
[4]Current Patent Assignee: PANMIRA PHARMACEUTICALS, INC. - WO2011/38086, 2011, A2 Location in patent: Page/Page column 102-103

30
[ 381-88-4 ]
[ 39687-95-1 ]
[ 1222094-91-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: isocyanoacetic acid methyl ester With sodium t-butanolate In tetrahydrofuran at -60 - -35℃; for 1.08333h; Inert atmosphere; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -45 - 25℃; for 2.41667h; Inert atmosphere; Stage #3: With hydrogenchloride; water In tetrahydrofuran for 1h; Inert atmosphere;

Reference： [1]Benhaim, Cyril; Bouchard, Luc; Pelletier, Guillaume; Sellstedt, John; Kristofova, Livia; Daigneault, Sylvain [Organic Letters, 2010, vol. 12, # 9, p. 2008 - 2011]

31
[ 381-88-4 ]
[ 106-37-6 ]
[ 1050445-45-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1.4-dibromobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78℃; for 0.25h;	8.1 To a solution of 1,4-dibromobenzene (2.5 g, 10.6 mmol) in THF (50 mL) at -78° C. was added n-BuLi (6.5 mL, 10 mmol; 1.6 M in hexanes) and the mixture was stirred at -78° C. for 15 min. 1,1,1-Trifluoro-2-butanone (1.3 g, 10 mmol) was then added. After further stirring for 15 min., the mixture was quenched with aqueous NH4Cl and extracted with Ethyl acetate. Purification by combi-flash chromatography (40 g column; eluted with hexanes-Ethyl acetate (10% -20%) in 20 min.; flow rate: 35 mL/min and collected 18 mL/fraction) to yield the title compound as a colorless liquid. 1H NMR (CD3COCD3) δ (ppm): 7.58 (m, 5H), 5.52 (s, 1H), 2.28 (m, 1H), 2.10 (m, 1H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2006/111440, 2006, A1 Location in patent: Page/Page column 19

32
[ 381-88-4 ]
(S)-1,1,1-trifluorobutan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1,1,1-trifluoro-2-butanone With (-)-diisopinocamphenylborane chloride at 20℃; for 10h; Inert atmosphere; Stage #2: With acetaldehyde In diethyl ether at 0 - 20℃; for 24h; Inert atmosphere; Stage #3: With sodium hydroxide In diethyl ether; water

Reference： [1]Location in patent: experimental part Yin, Wenyuan; Majumder, Samarpan; Clayton, Terry; Petrou, Steven; Vanlinn, Michael L.; Namjoshi, Ojas A.; Ma, Chunrong; Cromer, Brett A.; Roth, Bryan L.; Platt, Donna M.; Cook, James M. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 21, p. 7548 - 7564]

33
[ 381-88-4 ]
[ 7409-30-5 ]
C₁₁H₁₁F₃N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With acetic acid In chloroform Reflux;
	Stage #1: 1,1,1-trifluoro-2-butanone; p-nitrobenzylamine In chloroform at 0 - 20℃; for 0.333333h; Inert atmosphere; Molecular sieve; Stage #2: With acetic acid In chloroform for 3h; Inert atmosphere; Reflux;	2 Alkyl Trifluoromethyl Imines 1B-1F: General procedure: Under N2, to a flask charged with 4-NO2PhCH2NH2 (2.00 g, 13.0 mmol) and 4 MS (3.0 g) was added CHCl3 (20 mL). The corresponding trifluoromethyl ketone (10.0 mmol) was then added in one portion. The suspension was stirred at room temperature for 20 mins. HOAc (16.0 mmol) was added dropwise. Next the white suspension was moved to a 70° C. oil bath and refluxed for 3 h (1B-E) or 24 h (1F). After the suspension was cooled to room temperature, Hexanes (30 mL) was added. The suspension was filtered through a pad of deactivated silica (5 cm thick) and washed with Hexanes/Et2O=3/1 solution (100 mL). The filtrate was collected, and the solvent was removed. The residue was analyzed by 1H and 19F NMR, if lacking sufficient side products, the imine could be used directly. If not, the residue was applied to deactivated silica column chromatography (Hex/CH2Cl2=100/1 to Hex/CH2Cl2=10/1) to afford imine 1B-1F (29-75% yield). The spectral data of imines 1A-C and 1F were consistent with those reported in Wu & Deng, 2012, J. Am. Chem. Soc. 134:14334-14337.

Reference： [1]Wu, Yongwei; Deng, Li [Journal of the American Chemical Society, 2012, vol. 134, # 35, p. 14334 - 14337]
[2]Current Patent Assignee: BRANDEIS UNIVERSITY - US2020/48243, 2020, A1 Location in patent: Paragraph 0162; 0166-0167

34
[ 1721-93-3 ]
[ 381-88-4 ]
[ 1419293-90-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h;	General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield.

Reference： [1]Graves, Vincent B.; Shaikh, Abid [Tetrahedron Letters, 2013, vol. 54, # 7, p. 695 - 698]

35
[ 109-06-8 ]
[ 381-88-4 ]
[ 1419293-79-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h;	General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield.

Reference： [1]Graves, Vincent B.; Shaikh, Abid [Tetrahedron Letters, 2013, vol. 54, # 7, p. 695 - 698]

36
[ 91-63-4 ]
[ 381-88-4 ]
[ 1419293-67-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h;	General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield.
46%	With indium(III) chloride In <i>tert</i>-butyl alcohol at 60℃; for 24h;

Reference： [1]Graves, Vincent B.; Shaikh, Abid [Tetrahedron Letters, 2013, vol. 54, # 7, p. 695 - 698]
[2]Jamal, Zaini; Teo, Yong-Chua [RSC Advances, 2015, vol. 5, # 34, p. 26949 - 26953]

37
titanium(IV) tetraethanolate [ No CAS ]
[ 381-88-4 ]
[ 343338-28-3 ]
(S<SUB>S</SUB>)-N-(2-ethoxy-1,1,1-trifluorobutan-2-yl)(tert-butyl)sulfinamide [ No CAS ]
[ 1417739-53-7 ]

Yield	Reaction Conditions	Operation in experiment
1: 65% 2: 6%	In hexane at 20℃; for 48h;

Reference： [1]Grellepois, Fabienne [Journal of Organic Chemistry, 2013, vol. 78, # 3, p. 1127 - 1137]

38
[ 381-88-4 ]
[ 7677-24-9 ]
[ 1432731-23-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; zinc(II) chloride In water at 80℃; for 3h;	3.2 1.1. l-Trifluoro-2-f2H-tetrazol-5-vnbutan-2-ol (3-3 To l,l,l-trifluorobutan-2-one (5.0 g, 39.7 mmol, 1.0 equiv) was slowly addedtrimethylsilylcyanide (4.7 g, 47.6 mmol, 1.2 equiv) and the resulting mixture stirred overnight at ambient temperature. To the resulting mixture was added water (80 mL) followed by zinc chloride (5.4 g, 39.7 mmol, 1.0 equiv) and sodium azide (3.1 g, 47.1 mmol, 1.2 equiv) and the mixture was heated at 80°C for three hours. The mixture was cooled to room temperature and the precipitate was filtered and dried in vacuo to afford l,l,l-trifluoro-2-(2H-tetrazol-5-yl)butan-2-ol (3-3) as a white solid. LRMS m/z (M+H)+197.0 found, 197.1 required.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2013/66736, 2013, A1 Location in patent: Page/Page column 80

39
[ 381-88-4 ]
[ 104-94-9 ]
[ 126855-74-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	With montmorillonite K₁₀ In toluene at 130℃; for 4.5h; Microwave irradiation;

Reference： [1]Genoni, Andrea; Benaglia, Maurizio; Massolo, Elisabetta; Rossi, Sergio [Chemical Communications, 2013, vol. 49, # 75, p. 8365 - 8367]

40
[ 381-88-4 ]
[ 762-04-9 ]
[ 196929-78-9 ]
[ 1472660-60-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 1,1,1-trifluoro-2-butanone; (R)-2-methylpropane-2-sulfinamide With titanium(IV) isopropylate In hexane; toluene at 20℃; for 12h; Inert atmosphere; Stage #2: phosphonic acid diethyl ester In hexane; toluene at -40℃; Inert atmosphere; diastereoselective reaction;

Reference： [1]Wang, Lijing; Shen, Qilong; Lu, Long [Chinese Journal of Chemistry, 2013, vol. 31, # 7, p. 892 - 900]

41
[ 381-88-4 ]
[ 1576-35-8 ]
[ 1601477-03-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	In methanol at 60℃; for 2h; Inert atmosphere;

Reference： [1]Wang, Xi; Xu, Yan; Deng, Yifan; Zhou, Yujing; Feng, Jiajie; Ji, Guojing; Zhang, Yan; Wang, Jianbo [Chemistry - A European Journal, 2014, vol. 20, # 4, p. 961 - 965]

42
[ 381-88-4 ]
2-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)acetonitrile [ No CAS ]
[ 1579940-48-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; sulfur at 120 - 150℃; for 0.5h; Microwave irradiation; Inert atmosphere;	A.A6 Method A6: One-pot Gewald reaction using microwave conditions General procedure: Method A6: One-pot Gewald reaction using microwave conditions To the solution of the aldehyde or keton (1 mmol) in EtOH (1.5 mL) the heterocyclic acetonitrile derivative (1 mmol), sulfur (1 mmol) and N-methylmorpholine (1 mmol) are added, the reaction mixture heated in a microwave oven at 120-150 °C for 30 min. and then poured on 30 mL 10% aqueous NaHC03 solution and 30 mL EtOAc and the layers are separated. The aqueous layer is extracted a second time with 30 mL EtOAc. The organic layers are washed with 30 mL brine, dried over MgS04, filtered and evaporated. The compound is purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of w-heptane : EtOAc.
	With 4-methyl-morpholine; sulfur In ethanol at 120 - 150℃; for 0.5h; Microwave irradiation; Inert atmosphere;	A6 Method A6: One-Pot Gewald Reaction Using Microwave Conditions General procedure: Method A6: One-Pot Gewald Reaction Using Microwave Conditions [0295] To the solution of the aldehyde or keton (1 mmol) in EtOH (1.5 mL) the heterocyclic acetonitrile derivative (1 mmol), sulfur (1 mmol) and N-methylmorpholine (1 mmol) are added, the reaction mixture heated in a microwave oven at 120-150° C. for 30 min. and then poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers are separated. The aqueous layer is extracted a second time with 30 mL EtOAc. The organic layers are washed with 30 mL brine, dried over MgSO4, filtered and evaporated. The compound is purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/40938, 2014, A1 Location in patent: Page/Page column 66; 71
[2]Current Patent Assignee: ROCHE HOLDING AG - US2015/183778, 2015, A1 Location in patent: Paragraph 0295; 0297

43
[ 383-63-1 ]
[ 93-55-0 ]
[ 381-88-4 ]
[ 93-89-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 89 %Spectr. 2: 97%	Stage #1: ethyl trifluoroacetate, With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 1-phenyl-propan-1-one In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Schlenk technique; Reflux; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 0℃; for 0.25h; Inert atmosphere; Schlenk technique;	General procedure for ‘trifluoroacetic ester/ketone metathesis’ and the preparation of TFMKs General procedure: Under Ar atmosphere in a dry Schlenk tube, a mixture of NaH (6.0 mmol) and trifluoroacetate (6.0 mmol) was stirred in THF (5 mL) at room temperature for 10 min. To this mixture enolizable ketones (5.0 mmol) in THF (5 mL) was added dropwise at 0 °C under Ar atmosphere. After stirring for 2-6 h at reaction temperature, the reaction solution was cooled to 0 °C again and quenched with 6 mL of 1 mol/L HCl. After stirring for additional 15 min, the mixture was neutralized with saturated NaHCO3 solution. After usual workup, the residue was purified by chromatography on silica gel to afford the trifluoromethyl alkyl ketone products.

Reference： [1]Zhou, Yuhan; Yang, Dongmei; Luo, Gen; Zhao, Yilong; Luo, Yi; Xue, Na; Qu, Jingping [Tetrahedron, 2014, vol. 70, # 31, p. 4668 - 4674]

44
[ 925-90-6 ]
[ 104863-67-4 ]
[ 381-88-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	In tetrahydrofuran; at 0 - 20℃;Large scale;	General procedure: A mixture of the above <strong>[104863-67-4]2,2,2-trifluoro-N-methoxy-N-methylacetamide</strong> (3 Kg, 90 % purity, 0.017 kmol) in anhydrous THF (30 L) was cooled to 0 C and treated with 0.5 M Grignard reagent in THF (42 L). The reaction mixture was stirred at 0 C for 0.5 h and allowed to warm to room temperature. The resulting mixture was stirred at room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate three times. The organic layers were combined and washed with water and brine, dried over MgSO4 and filtered. After rectification, the resulting α-trifluoromethylated ketones were obtained (95 % purity, 90 % yield).

Reference： [1]Asian Journal of Chemistry,2015,vol. 27,p. 2406 - 2408
[2]RSC Advances,2013,vol. 3,p. 9820 - 9828

45
[ 381-88-4 ]
[ 100-46-9 ]
[ 1225210-27-4 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In toluene at 0℃; Reflux;

Reference： [1]Cheng, Guilin; Xia, Bo; Wu, Qi; Lin, Xianfu [RSC Advances, 2013, vol. 3, # 25, p. 9820 - 9828]

46
[ 381-88-4 ]
[ 100-52-7 ]
1,1,1-trifluoro-3-methyl-4-phenylbut-3-en-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With amine