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Chemical Structure| 15996-84-6 Chemical Structure| 15996-84-6

Structure of 15996-84-6

Chemical Structure| 15996-84-6

1-(4-(Trifluoromethyl)phenyl)ethanamine

CAS No.: 15996-84-6

4.5 *For Research Use Only !

Cat. No.: A204729 Purity: 97%

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Product Details of [ 15996-84-6 ]

CAS No. :15996-84-6
Formula : C9H10F3N
M.W : 189.18
SMILES Code : CC(N)C1=CC=C(C=C1)C(F)(F)F
MDL No. :MFCD04038878

Safety of [ 15996-84-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H319
Precautionary Statements:P301+P310-P305+P351+P338
Class:6.1
UN#:2811
Packing Group:

Application In Synthesis of [ 15996-84-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 15996-84-6 ]

[ 15996-84-6 ] Synthesis Path-Downstream   1~38

  • 1
  • [ 15996-83-5 ]
  • [ 15996-84-6 ]
YieldReaction ConditionsOperation in experiment
With ammonia; hydrogen;palladium 10% on activated carbon; In methanol; water; under 3102.97 Torr; for 2h; EXAMPLE 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
  • 2
  • [ 1188-21-2 ]
  • [ 15996-84-6 ]
  • [ 84499-82-1 ]
  • 3
  • [ 709-63-7 ]
  • [ 15996-84-6 ]
YieldReaction ConditionsOperation in experiment
68% Ti(OiPr)4 (31.5 mL, 106 mmol) was added to (p-trifluoromethyl)acetophenone 108 (10.0 g, 53.1 mmol) in NH3 (2.0 M in EtOH, 133 mL) and the resultant mixture was stirred at rt for 6 h. NaBH4 (3.01 g, 79.7 mmol) was added at 0 C, and the resultant suspension was stirred at rt for 3 h, then poured into 2.0 M aq NH4OH (200 mL). The resultant suspension was filtered (eluent EtOAc) and the aqueous layer was extracted with EtOAc (2*80 mL). The combined organic extracts were extracted with 1.0 M aq HCl (3*50 mL) and the combined aqueous extracts were washed with EtOAc (3*30 mL), treated with 2.0 M aq NaOH until pH>8 was observed, then extracted with EtOAc (4*50 mL). The combined organic extracts were washed with brine (200 mL), then dried and concentrated in vacuo to give (RS)-117 as a pale yellow oil (6.84 g, 68%);43 δH (400 MHz, CDCl3) 1.40 (3H, d, J 6.6, C(α)Me), 1.59 (2H, br s, NH2), 4.20 (1H, q, J 6.6, C(α)H), 7.48 (2H, d, J 7.8, C(2)H, C(6)H), 7.59 (2H, d, J 7.8, C(3)H, C(5)H).
52% A mixture of 1-(4-(trifluoromethyl)phenyl)ethanone (400 mg, 2.13 mmol), Ti(O-i-Pr)4 (1.25 mL, ∼4.25 mmol) and ammonia in EtOH (2 M, 5.30 mL, ∼10.6 mmol) was stirred under argon at room temperature for 24 h NaBH4 (120 mg, 3.19 mmol) was then added, and the resulting mixture was stirred for another 24 h. The pH of the reaction mixture was adjusted to pH 2 using HCl (6 M), and washed with tert-butyl methyl ether (TBME) (3 × 20 mL). Using NaOH (pellets) the pH was adjusted to ca 10, and the mixture was extracted with TBME (6 × 30 mL). The combined organic phase was dried over MgSO4, and the solvent was removed under reduced pressure to give 210 mg (1.11 mmol, 52%) of a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.58 (m, 2H), 7.46 (m, 2H), 4.19 (q, J = 6.7, 1H), 1.38 (d, J = 6.7, 3H), 1.51 (s, 2H, NH2). 13C NMR (100 MHz, CDCl3) δ: 152.1 (q, J = 1.1), 129.4 (q, J = 31.5), 126.5 (2C), 125.8 (q, J = 3.8, 2C), 124.6 (q, J = 270.9), 51.4, 25.1.
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; ammonium formate; In methanol; at 70℃; for 7h;Inert atmosphere; General procedure: The corresponding ketone (20 mmol, 1.0 eq) and CH3OH (20 mL) were added to a 250 mL Schlenk tube containing [RhCp*Cl2]2 (61.8 mg, 100 μmol, 0.005 equiv) and HCOONH4 (6.36 g, 100 mmol, 5.0eq). The brown mixture was frozen, and the whole system was evacuated. The system was closed and then stirred at 70 C for 7 h. After the dark green resulting solution was cooled to room temperature, 1M aqueous HCl solution (38.4 mL) was added, and the mixture was washed twice with CH2Cl2 (5 mL) to remove the neutral compounds. After addition of a cold 12 M aqueous NaOH solution (3.6 mL) to the aqueous layer, the mixture was extracted six times with CH2Cl2 (12 mL). The combined organic layers were dried over anhydrous Na2SO4. Filtration and evaporation under reduced pressure gave crude amine,which was used without purification. All the crude corresponding amine was dissolved in dichloromethane (50 mL), and TCCA (trichloroisocyanuric acid) (3.2 g, 14 mmol) was added in a250 ml round-bottom flask at 0 C. Then, the mixture was stirred at ambient temperature during 1 h. Triethylamine (6.0 g, 6 mol) dissolved in dichloromethane (50 mL) was added, and the resulting mixture was washed with water (200 mL) and hydrochloric acid (1 M, 200 mL)successively. The organic layer was dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification by column chromatography on silica gel (n-hexane/EtOAc:40/1) afforded pure product.
  • 4
  • (R)-(-)-O-acetylmandelic acid [ No CAS ]
  • [ 15996-84-6 ]
  • [ 581812-92-2 ]
  • [ 581812-91-1 ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide; at 20℃; EXAMPLE 138A (1R)-2-oxo-1-phenyl-2-({1-[4-(trifluoromethyl)phenyl]ethyl}amino)ethyl Acetate 1-[4-(Trifluoromethyl)phenyl]ethanamine (37.5 g, 198.4 mmol) and (R)-acetylmandelic acid (40.4 g, 208.3 mmol, 1.05 eq.) were combined in DMAP (0.7 g, 5.7 mmol) and treated with DCC (45.0 g, 218 mmol). After stirring overnight at ambient temperature, the mixture was filtered through a plug of silica. The filtrate was concentrated and the residue was purified by chromatography on Biotage Flash 75 column (ethyl acetate:hexanes, 25:75) to provide a faster running diastereomer and a slower running diastereomer. (fast diastereomer) 1H NMR (300 MHz, CDCl3) 7.58 (d, 2H), 7.39 (m, 7H), 6.30 broad (d, 1H), 6.08 (s, 1H), 5.18 (m, 1H), 2.20 (s, 3H), 1.29 (d, 3H); MS (DCI/NH3) m/e 366 (M+H)+. (slow diastereomer) 1H NMR (300 MHz, CDCl3) 7.58 (d, 2H), 7.40 (m, 5H), 7.31 (d, 2H), 6.21 (broad d, 1H), 6.06 (s, 1H), 5.18 (m, 1H), 2.20 (s, 3H), 1.50 (d, 3H); MS (DCI/NH3) m/e 366 (M+H)+.
  • 5
  • [ 15996-84-6 ]
  • (-)-[(Ph-PPY*COMe)(+)Cl(-)] [ No CAS ]
  • (S)-N-(1-(4-(trifluoromethyl)phenyl)ethyl)acetamide [ No CAS ]
  • (R)-N-[1-(4-trifluoromethylphenyl)ethyl]acetamide [ No CAS ]
  • 6
  • [ 15996-84-6 ]
  • carbonic acid 4-<i>tert</i>-butyl-2-naphthalen-2-yl-oxazol-5-yl ester methyl ester [ No CAS ]
  • [(S)-1-(4-Trifluoromethyl-phenyl)-ethyl]-carbamic acid methyl ester [ No CAS ]
  • [(R)-1-(4-Trifluoromethyl-phenyl)-ethyl]-carbamic acid methyl ester [ No CAS ]
  • 7
  • [1-(4-<i>tert</i>-butyl-phenyl)-ethyl]-[1-(4-trifluoromethyl-phenyl)-ethyl]-amine [ No CAS ]
  • [ 89538-65-8 ]
  • [ 15996-84-6 ]
  • 8
  • [ 15996-84-6 ]
  • [ 151067-74-2 ]
  • 1-(7-hydroxy-naphthalen-1-yl)-3-[1-(4-trifluoromethyl-phenyl)-ethyl]-urea [ No CAS ]
  • 9
  • [ 108-21-4 ]
  • [ 15996-84-6 ]
  • (R)-N-[1-(4-trifluoromethylphenyl)ethyl]acetamide [ No CAS ]
  • 10
  • [ 3938-96-3 ]
  • [ 15996-84-6 ]
  • 2-methoxy-N-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)acetamide [ No CAS ]
  • 11
  • [ 15996-84-6 ]
  • [ 141-78-6 ]
  • (R)-N-[1-(4-trifluoromethylphenyl)ethyl]acetamide [ No CAS ]
  • 12
  • 2-(3,4,6-trifluorobenzoyl)-3-(dimethylamino)acrylonitrile [ No CAS ]
  • [ 15996-84-6 ]
  • C19H12F6N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% In methanol; at 0 - 20℃; for 96 - 120h; To a stirred solution of compound 2b.4 (2.0 g, 7.8 mmol) in methanol (60 mL) was added 4-trifruorornethyl-α-methyl benzyl amine 2b.5 (1.6 g, 9.4 mmol) under nitrogen atmosphere. The reaction mixture stirred at room temperature for 4 to 5 days. Once the reaction was completed then solvent was removed under reduced pressure. The residue was purified by flash column chromatography eluting with 15 % ethyl acetate in n-hexane to provide compound 2b.6 (2.6 g, 92%). 1H-NMR (DMSO-^)δ 10.98 (1/2H, m, Ar-H), 9.94 (1/2H, m, Ar-H), 8.24-7.98 (IH, m, Ar-H), 7.80-7.56 (6H, m, Ar-H), 5.02 (IH, m, -CH), 1.72-1.47 (3H, 2 x d,-CH3). EIMS (m/z): 399.4 (M + H) +
  • 13
  • diethyl [3-methoxypro-2-enylidene]malonate [ No CAS ]
  • [ 15996-84-6 ]
  • [ 1001413-61-1 ]
YieldReaction ConditionsOperation in experiment
In iso-butanol; at 110℃; for 16h; The diethyl [3-methoxypro-2-enylidene]malonate (1.0 g, 4.4 mmol), Compound 7.1, was added to a 2-dram vial in 2 ml of s-BuOH. To the mixture was added l-(4- trifluoromethyl-phenyl)-ethylamine (mixture of enantiomers) (0.74 g, 4.6 mmole). The reaction mixture was heated to 1100C for 16 hours. When the reaction was completed, the solvent was removed using GeneVac HT-12 to give Compound 51.1. ES (+) MS m/e = 340 (M+l).
  • 14
  • [ 51019-43-3 ]
  • [ 15996-84-6 ]
  • [ 581812-92-2 ]
  • [ 581812-91-1 ]
YieldReaction ConditionsOperation in experiment
33%; 36% With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 16h; DCC (2.35 g, 12.1 mmol) and DMAP (50 mg) were added to a stirred solution of (RS)-117 (2.29 g, 12.1 mmol) and (R)-O-acetylmandelic acid (2.35 g, 12.1 mmol, >99:1 er) in CH2Cl2 (60 mL) at 0 C and the resultant mixture was stirred at rt for 16 h. The reaction mixture was filtered and the filtrate was washed sequentially with 1.0 M aq HCl (40 mL), satd aq NaHCO3 (40 mL) and brine (40 mL), then dried and concentrated in vacuo. Purification via flash column chromatography (eluent 30-40 C petrol/EtOAc, 2:1, 1% Et3N) gave 119 as a white solid (1.58 g, 36%, >99:1 dr); mp 132.5-133.5 C; νmax (ATR) 3292 (N-H), 1742, 1662 (C=O), 1327 (C-F); [α]D20 -153.0 (c 1.0 in MeOH); δH (500 MHz, CDCl3) 1.40 (3H, d, J 7.0, C(α)Me), 2.13 (3H, s, COMe), 4.87 (1H, br s, NH), 5.00 (1H, q, J 7.0, C(α)H), 5.94 (1H, s, C(2)H), 7.33-7.39 (3H, m, C(2')H, C(6')H, Ph), 7.48-7.53 (4H, m, Ph), 7.58 (2H, d, J 8.2, C(3')H, C(5')H); δC (125 MHz, CDCl3) 20.8 (COMe), 22.1 (C(α)Me), 50.0 (C(α)), 77.2 (C(2)), 125.9 (q, J 269.9, CF3), 126.4 (q, J 3.8, C(3'), C(5')), 127.9 (C(2'), C(6')), 128.7 (o-Ph), 129.8 (m-Ph), 130.2 (p-Ph), 130.3 (q, J 31.5, C(4')), 136.8 (i-Ph), 149.5 (C(1')), 171.0 (C(1)), 172.1 (COMe); δF (377 MHz, CDCl3) -63.9 (CF3); m/z (ESI+) 388 ([M+Na]+, 100%); HRMS (ESI+) ([M+Na]+) requires 388.1131; found 388.1122. Further elution gave 118 as a white solid (1.46 g, 33%, >99:1 dr); mp 118-120 C; νmax (ATR) 3291 (N-H), 1744, 1663 (C=O), 1327 (C-F); [α]D20 -17.0 (c 1.0 in MeOH); δH (500 MHz, CDCl3) 1.47 (3H, d, J 7.0, C(α)Me), 2.15 (3H, s, COMe), 4.87 (1H, br s, NH), 5.06 (1H, q, J 7.0, C(α)H), 5.94 (1H, s, C(2)H), 7.24 (2H, d, J 8.4, C(2')H, C(6')H), 7.34-7.38 (3H, m, Ph), 7.44-7.49 (4H, m, C(3')H, C(5')H, Ph); δC (125 MHz, CDCl3) 20.8 (COMe), 22.0 (C(α)Me), 50.0 (C(α)), 77.1 (C(2)), 125.7 (q, J 270.8, CF3), 126.4 (q, J 3.8, C(3'), C(5')), 127.6 (C(2'), C(6')), 128.8 (o-Ph), 129.8 (m-Ph), 130.2 (p-Ph), 130.3 (q, J 32.4, C(4')), 136.7 (i-Ph), 149.5 (C(1')), 170.9 (C(1)), 172.1 (COMe); δF (377 MHz, CDCl3) -63.7 (CF3); m/z (ESI+) 388 ([M+Na]+, 100%); HRMS (ESI+) ([M+Na]+) requires 388.1131; found 388.1120. A 57:43 mixture of 118 and 119, respectively, was also recovered as a white solid (812 mg, 18%).
  • 16
  • [ 902131-30-0 ]
  • [ 15996-84-6 ]
  • C19H17F3N4O3 [ No CAS ]
  • 17
  • [ 15996-84-6 ]
  • C17H15F3N4O [ No CAS ]
  • 18
  • [ 15996-84-6 ]
  • C19H17F3N4O3 [ No CAS ]
  • 19
  • [ 15996-84-6 ]
  • C17H15F3N4O [ No CAS ]
  • 20
  • [ 15996-84-6 ]
  • C19H17F3N4O3 [ No CAS ]
  • 21
  • [ 15996-84-6 ]
  • C17H15F3N4O [ No CAS ]
  • 24
  • [ 791068-41-2 ]
  • [ 15996-84-6 ]
  • [ 791068-49-0 ]
YieldReaction ConditionsOperation in experiment
With sodium cyanoborohydride; In dichloromethane; at 20℃; for 16h; A mixture of 4-methyl-3-oxo-3, 4-dihydro-quinoxaline-2-carbaldehyde (100 mg), sodium cyanoborohydride (0.050 g, 1.5 eq), and 1- (4-TRIFLUOROMETHYL-PHENYL)-ETHYLAMINE (100 mg) in dry CH2C12 (1.5 mL) was stirred at rt under nitrogen for 16h. The reaction mixture was basified with a sat. NAHCO3 solution, extracted CH2C12. The combined organic extracts were dried (MGS04), filtered and concentrated in vacuo to give a crude oil. FC (CH2C12/MEOH : 95/5) gave the title compound as a brown oil. LC-MS: RT = 0.77 min. m/z = 362 (M + 1).
  • 25
  • [ 15996-83-5 ]
  • [ 15996-84-6 ]
YieldReaction ConditionsOperation in experiment
With ammonia; hydrogen;palladium-carbon; In methanol; EXAMPLE 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
With ammonia; hydrogen;palladium-carbon; In methanol; Example 136B 1-[4-(trifluoromethyl)phenyl]ethanamine The product from Example 136A (21.0 g, 100 mmol) in MeOH (220 mL) and ammonia (30 mL) was treated with 10% Pd/C under 60 psi of hydrogen gas for 2 hours. The mixture was filtered and the filtrate was concentrated to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 7.60 (q, 4H), 4.07 (q, 1H), 3.28 (broad s, 2H), 1.24 (d, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
  • 26
  • [ 852241-17-9 ]
  • [ 15996-84-6 ]
YieldReaction ConditionsOperation in experiment
With aqueous HBr; In water; EXAMPLE 138B (-) 1-[4-(trifluoromethyl)phenyl]ethanamine The faster running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. 94% ee (by Mosher amide NMR). [α]D -19.1 (c 1.15; MeOH); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.65 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
With aqueous HBr; In water; EXAMPLE 138C (+) 1-[4-(trifluoromethyl)phenyl]ethanamine The slower running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. [α]D +20.5 (c 1.47; MeOH). 94% ee (Mosher amide NMR); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.60 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
With aqueous HBr; In water; Example 138B (-) 1-[4-(trifluoromethyl)phenyl]ethanamine The faster running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. 94% ee (by Mosher amide NMR). [α]D -19.1 (c 1.15; MeOH); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.65 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+.
With aqueous HBr; In water; Example 138C (+) 1-[4-(trifluoromethyl)phenyl]ethanamine The slower running diastereomer from Example 138A (29.2 g, 80 mmol) was treated with 48% aqueous HBr (350 mL) and water (50 mL) and was refluxed for 16 hours. The mixture was cooled and extracted with diethyl ether. The aqueous phase was basified with 2N NaOH (pH 12-13) and extracted with diethyl ether. The organic phase was concentrated to provide the title compound. [α]D +20.5 (c 1.47; MeOH). 94% ee (Mosher amide NMR); 1H NMR (300 MHz, CDCl3) 7.60 (d, 2H), 7.47 (d, 2H), 4.20 (m, 1H), 1.60 (br s, 2H), 1.40 (s, 3H); MS (DCI/NH3) m/e 190 (M+H)+.

  • 27
  • [ 455-18-5 ]
  • [ 75-16-1 ]
  • [ 15996-84-6 ]
  • 28
  • [ 6290-49-9 ]
  • [ 15996-84-6 ]
  • 2-methoxy-N-((R)-1-(4-(trifluoromethyl)phenyl)ethyl)acetamide [ No CAS ]
  • 29
  • [ 15996-84-6 ]
  • [ 98-88-4 ]
  • N-(1-(4-(trifluoromethyl)phenyl)ethyl)benzamide [ No CAS ]
  • 30
  • [ 15996-84-6 ]
  • [ 530-62-1 ]
  • [ 91188-13-5 ]
  • [ 920320-49-6 ]
YieldReaction ConditionsOperation in experiment
67% To a solution of l-[4-(trifluoromethyl)phenyl]ethylamine (1.Og, 5.2 mmol) in dichloromethane (20 ml) at 3O0C was added a suspension of 1,1 '-carbonyl diimidazole (0.86g, 5.2mmol) in dichloromethane (7 ml) and the reaction was stirred at 3O0C for 1 hour. A suspension of azetidine-3-yl-carbamic acid terf-butyl ester (0.89g, 5.2mmol) in dichloromethane (5ml) was added and the reaction stirred at 30 for 5 hours. The reaction was cooled to room temperature (r.t.) and the product obtained by filtration as a white solid. Yield 1.35 g (67%): HPLC retention time, 3.56min (Solvent: CH3CN/H2O/0.05% NH3, 5-95% gradient H2O-6min. Column: Xterra 50 x 4.60 i.d., Cl 8 reverse phase. Flow rate: 1.5mL/min.). Mass spectrum (ES+) m/z 388 (M + H).
  • 31
  • [ 173459-03-5 ]
  • [ 15996-84-6 ]
  • [ 1350639-68-7 ]
YieldReaction ConditionsOperation in experiment
75% In butan-1-ol; at 145℃; for 24h;Inert atmosphere; General procedure: The following is representative: 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (7a) (275 mg, 1.06 mmol) and (R)-1-phenylethanamine (0.44 mL, ∼3.5 mmol) were added to a dry round bottle flask containing 1-butanol (3.5 mL) under argon atmosphere. The mixture was heated at 145 C for 24 h. The precipitate formed upon cooling to rt. was isolated by filtration, washed with diethyl ether (25 mL) and dried resulting in a solid.
In butan-1-ol; at 145℃; General procedure: Compound 1a-d or 54 (1 mmol) was mixed with the selected amine, 2-25, (3 mmol) and n-butanol (5 ml) and agitated at145 C for 14-24 h. Then the mixture was cooled to 22 C, dilutedwith water (15 ml) and ethyl acetate (40 ml). After phase separation,the water phase was back extracted with more ethyl acetate(2 10 ml). The combined organic phases were washed with brine(10 ml), dried over anhydrous Na2SO4, filtered and concentrated invacuo, before the crude mixture was purified as specified for eachindividual compound
In butan-1-ol; at 145℃; for 24h;Inert atmosphere; General procedure: The following is representative: 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (14) (275 mg, 1.06 mmol) and (S)-1-phenylethanamine ((S)-19i) (0.44 mL, ∼3.5 mmol) were added to a dry round bottle flask containing 1-butanol (3.5 mL) under argon atmosphere. The mixture was heated at 145 C for 24 h. The precipitate formed upon cooling to rt. was isolated by filtration, washed with diethyl ether (25 mL) and dried resulting in a solid.
  • 32
  • [ 173459-03-5 ]
  • [ 15996-84-6 ]
  • [ 1350639-83-6 ]
YieldReaction ConditionsOperation in experiment
85% General procedure: Example 3 - General procedure for the transfer hydroqenative reductive amination using ammonium formate Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μηιοΙ) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCI solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum.
85% General procedure: Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2 ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C. under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μmol) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C. for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCl solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum.This general reaction procedure was then applied to the following reductive amination reactions using catalyst 2c in methanol, the results for which are presented in Table 4A below
56% With aluminium(III) triflate; (carbonyl)(chloro)(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; hydrogen; 1,2-bis-(diphenylphosphino)ethane; at 120℃; for 16h;Autoclave; General procedure: Isolated yields (isolated from the reaction mixture by column chromatography). Examples 17-29 show that various carbonyl compounds can be converted to the corresponding primary amines in good yields using the inventive method.
General procedure: Example 4 - General procedure for transfer hvdrogenative reductive ami nation using ammonium formate [00141 ] Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μηιοΙ) in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCI solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum.
With formic acid; C25H28ClIrN2O3; ammonium acetate; triethylamine; In 2,2,2-trifluoroethanol; at 80℃; General procedure: Ketone (0.5 mmol) and HCOONH4 (5 mmol) were dissolved in MeOH (2 ml) in a carousel reaction tube. The mixture was than degassed and stirred for 10 minutes at 80 C. under nitrogen. HCOOH/NEt3 azeotrope (0.5 ml) and catalyst solution (1 ml) (prepared by dissolving catalyst (0.5 μamp in MeOH (1 ml)) were then introduced. The resulting mixture was stirred at 80 C. for the time indicated. The reaction was quenched with water, basified with aqueous KOH solution and extracted with DCM. The solvent was then removed under vacuum. The crude product was dissolved in ethanol (10 ml) and 6 N HCl solution (5 ml) was than added. The mixture was refluxed for 6 hrs. Ethanol was then removed under vacuum and the resultant aqueous layer was washed with ethyl acetate to remove impurities. The aqueous layer was basified with a KOH solution and extracted with DCM. The organic layers were combined and dried over sodium sulphate. The final product was obtained after the evaporation of solvent under vacuum.

  • 34
  • [ 15996-84-6 ]
  • (R)-2-(methylthio)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
  • (S)-2-(methylthio)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
  • 35
  • [ 15996-84-6 ]
  • (R)-2-(methylsulfonyl)-6-oxo-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
  • 36
  • [ 15996-84-6 ]
  • 2-(4-fluorobenzyl)-6-oxo-N-{(1R)-1-[4-(trifluoromethyl)phenyl]ethyl}-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
  • 37
  • [ 6314-14-3 ]
  • [ 15996-84-6 ]
  • C15H14F3N3O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; General procedure: The racemic mixture of the title compound obtained using procedure described in scheme A and Example 8 was resolved by chiral separation on OJ column with 15% ]4eOH/C02 to afford isomerA (faster eluting), (R)2-.(inethylthio).-6oxo-.N.( I (4-(trif1uoromethyl)phenyl)ethy1)- I ,6-.dihydro pyrimidine.-4-carboxamide and isomer B (slower eluting), (S)-2-methyithio)..6.-oxoN-(l (4.. (trifluoromethyi)phenyl)ethyl)-i ,6dihydro pyrimidine.-4carboxamide. MS: 358.1 (M+H).
  • 38
  • [ 15996-84-6 ]
  • [ 140923-27-9 ]
  • C18H25F3N2O3 [ No CAS ]
 

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