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Chemical Structure| 371917-17-8 Chemical Structure| 371917-17-8

Structure of 371917-17-8

Chemical Structure| 371917-17-8

(1-(Trifluoromethyl)cyclopropyl)methanol

CAS No.: 371917-17-8

4.5 *For Research Use Only !

Cat. No.: A910910 Purity: 98%

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Product Details of [ 371917-17-8 ]

CAS No. :371917-17-8
Formula : C5H7F3O
M.W : 140.10
SMILES Code : OCC1(C(F)(F)F)CC1
MDL No. :MFCD16990760
InChI Key :YYWSKSKIJXVNTH-UHFFFAOYSA-N
Pubchem ID :50990661

Safety of [ 371917-17-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P233-P240-P241-P242-P243-P280-P303+P361+P353-P370+P378-P403+P235-P501
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 371917-17-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 25.13
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.66
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.26
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.52
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.32
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.95
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.74

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.37
Solubility 5.97 mg/ml ; 0.0426 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.28
Solubility 7.29 mg/ml ; 0.0521 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.39
Solubility 5.73 mg/ml ; 0.0409 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.26 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.1

Application In Synthesis of [ 371917-17-8 ]

* 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 [ 371917-17-8 ]

[ 371917-17-8 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 277756-43-1 ]
  • [ 371917-17-8 ]
  • 2
  • [ 98-59-9 ]
  • [ 371917-17-8 ]
  • [ 865833-72-3 ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine;dmap; In dichloromethane; at 20℃; for 12h;Inert atmosphere; Step 2: Synthesis of (l-(trifluoromethyl)cyclopropyl)methyl 4- methylbenzenesulfonate:To a stirred solution of (l-(trifluoromethyl)cyclopropyl)methanol (step 1, 4.5 g) in dichloromethane (50 ml), Et3N (13.5 ml) was added at 0 C under N2 atmosphere followed by TsCl (9.1 g) and catalytic amount of DMAP. The reaction mixture was allowed to room temperature and stirred for about 12 hours. After completion of the reaction (monitored by 1H- NMR), reaction mixture was diluted with dichloromethane and organic layer was washed with saturated aq. NHUC1 solution, brine and dried over anhydrous sodium sulphate and concentrated to give the residue. The crude product was purified via silica gel column chromatography with EtOAc and n-Hexane (1:39) to afford the title compound as liquid (8.2 g). Yield: 86 %; 1H NMR (CDC13, 300 MHz): δ 7.79 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 4.09 (s, 2H), 2.46 (s, 2H), 1.14- 1.10 (m, 2H), 0.85- 0.84 (m, 2H); ES Mass: (M+ Na) 317.08.
81% With dmap; triethylamine; In dichloromethane; at 20℃; Treat a solution of (l-(trifluoromethyl)cyclopropyl)methanol (7 g, 50 mmol) and p-toluenesulfonyl chloride (10.4 g, 55 mmol) in DCM (100 mL) with TEA (10 g, 100 mmol) and 4-dimethylaminopyridine (DMAP) (0.6 g, 5 mmol) and stir at RT overnight. Wash successively with 2 M HC1, satd. NaHC03, and brine, dry over Na2S04 and concentrate to give the title compound (12 g, 81%). 1H NMR (400 MHz, DMSO-d6): δ 7.79 (d, J = 8.0 Hz, 2 H), 7.50 (d, J = 8.0 Hz, 2 H), 4.13 (s, 2 H), 2.43 (s, 3 H), 1.08-1.05 (m, 2 H), 0.96-0.94 (m, 2 H).
75.2% With triethylamine; In dichloromethane; at 20℃; A solution of <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> (5.0 g, 35.7 mmol), Et3N (7.2 g, 71.4 mmol) and TsCl (7.5 g, 39.3 mmol) in DCM (60 mL) was stirred at RT overnight. The mixture was concentrated under vacuum and the residue was purified by silica gel column chromatography (PE:EA=10:1) to give (1-(trifluoromethyl)cyclopropyl)methyl 4- methylbenzenesulfonate (7.9 g, 75.2%) as a colorless oil.1H NMR (400 MHz, DMSO-d6) d 7.77 (m, 2H), 7.48 (m, 2H), 4.16 (s, 2H), 2.41 (s, 3H), 1.04 (m, 2H), 0.92 (m, 2H).
70% With dmap; triethylamine; In dichloromethane; at 20℃; for 12h; [01043]A mixture of [1-(trifluoromethyl)cyclopropyl]methanol (2.6 g, 18.56 mmol, 1.00 equiv), dichloromethane (30 mL), TEA (5.63 g, 55.64 mmol, 3.00 equiv), 4-dimethylaminopyridine (2271.86 mmol, 0.10 equiv), and 4-methylbenzene-1-sulfonyl chloride (4.26 g, 22.36 mmol, 1.20 equiv) was stirred for 12 h at room temperature. The resulting solution was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel colunm eluting with ethyl acetate/petroleum ether to afford the title compound (3.8 g, 70%) as colorless oil. GCMS [mlz] 294.
70% With triethylamine; In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran; at 20℃; for 2h;Cooling with ice; To a solution of <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> (350 mg, 2.5 mmol) and TEA (757.5 mg, 7.5 mmol) in DCM (5 mL) in an ice-water bath, was added TsCl (573 mg, 3.0 mmol) in portions. The mixture was allowed to warm to room temperature and stirred for 2 h. The solvent was removed under reduced pressure. The residue was purified by prep-HPLC to give the product as a colorless oil (0.52 g, yield: 70%).
66% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; A 0 C. solution of <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> (2.46 g, 17.56 mmol), TEA (2.94 mL, 21.1 mmol) and DMAP (0.215 g, 1.76 mmol) in DCM (35 mL) was treated with p-toluenesulfonyl chloride (3.38 g, 17.7 mmol), allowed to warm to RT and stirred overnight. The mixture was treated with additional DCM, washed with 2N HCl (3×), followed by satd. NaHCO3, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford (1-(trifluoromethyl)cyclopropyl)methyl 4-methylbenzenesulfonate (3.42 g, 66%). 1H NMR (400 MHz, DMSO-d6): δ 7.77 (m, 2H), 7.48 (m, 2H), 4.16 (s, 2H), 2.41 (s, 3H), 1.04 (m, 2H), 0.92 (m, 2H); MS (ESI) m/z: 295.1 (M+H+).
49% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; Step 2: p-Toluenesulfonyl chloride (9.6 g, 50.35 mmol) was added at 0 C. to a mixture of (1-trifluoromethyl-cyclopropyl)-methanol (7 g, 49.96 mmol), triethylamine (7.7 mL, 55.24 mmol) and DMAP (0.61 g, 4.996 mmol) in 100 mL of DCM. The resulting mixture was stirred at 0 C. to RT overnight before being washed with aqueous 1M HCl. The aqueous layer was back extracted twice with DCM. The combined organic layers were dried (Na2SO4), filtered, and evaporated. The residue was purified by SiO2 flash chromatography (120 g SiO2, hexanes/[hexanes/Et2O 8/2] 100 to 0% hexanes) to give 7.26 g of toluene-4-sulfonic acid 1-trifluoromethyl-cyclopropylmethyl ester (49% yield).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; Preparation 52; [1- (trifluoromethyl) cyclopropyl] methyl 4-methylbenzenesulfonate; To a solution of 1- (trifluoromethyl) cyclopropyl] methanol (J. Fluorine Chem. , 2001,109, 2,95, 8.18 g, 58.4 mmol) in dichloromethane (50 ml), at 0C, was added triethylamine (50 ml), 4-dimethylaminopyridine (713 mg, 5.84 mmol) and p-toluenesulphonyl chloride (11.1 g, 58.4 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between diethyl ether (250ml) and hydrochloric acid (0. 5M, 100 ml). The two layers were separated and the aqueous phase was extracted with diethyl ether (100 ml). The combined organic phases were washed with saturated aqueous sodium hydrogencarbonate solution (50 ml) and brine (50 ml), dried (MgS04) and concentrated in vacuo. The residue was purified using a BiotageT" Flash 40 system with gradient elution, diethyl ether: cyclohexane [5: 95 to 20: 80]. The appropriate fractions were combined and concentrated to give the titled compound (11.8 g). 'H-NMR (CDCI3) : 0.81-0. 89 (2H), 1.09-1. 16 (2H), 2.44-2. 48 (3H), 4.09-4. 12 (2H), 7.33-7. 39 (2H), 7.77-7. 82 (2H)
With pyridine; In dichloromethane; at 20 - 50℃; for 5h; The residue was dissolved in dichloromethane (4ml), pyridine (0.48ml, 6mmol) and p- toluenesulfonyl chloride (1.1g, 6mmol) were added. The mixture was stirred for 3 hours at room temperature, warmed at 50C for 2 hours, cooled to room temperature, then evaporated. Water was added then 2M hydrochloric acid and the mixture was extracted with diethyl ether (x3). combined organic extracts were dried (MgS04) and evaporated to dryness to give 100mg of the title compound. 1HNMR CDCI3 δ: 0.82-0.86(2H,m), 1.10-1.13(2H,m), 2.46 (3H.s), 4.09 (2H,s), 7.35 (2H,d), 7.78 (2H,d).
With dmap; In dichloromethane; at 25℃; for 18h; To a round-bottom flask were added (1- (trifluoromethyl) cyclopropyl) methanol (4200 mg, 30.0 mmol) , DCM (120 mL) , 4-methylbenzene-1-sulfonyl chloride (7430 mg, 39.0 mmol) , N, N-dimethylpyridin-4-amine (366 mg, 3.00 mmol) and N, N-dimethylpyridin-4-amine (366 mg, 3.00 mmol) . The reaction mixture was stirred for 18 h at 25 . The mixture was concentrated in vacuum and the residue was purified by normal phase chromatography (ISCO, SiO2, 40 g Agela Flash column, 0-5EA/PE, 40 min, dry loaded) to give the title compound.1H NMR (CDCl3, 400 MHz) : δ 7.77 (d, J 8.22 Hz, 2H) , 7.47 (d, J 7.83 Hz, 2H) , 4.16 (s, 2H) , 2.40 (s, 3H) , 1.03 (s, 2H) , 0.92 (bs, 2H) .
7.3 g With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 15h;Inert atmosphere; To a stirred solution of <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> (5.11 g, 38.96 mmol) in anhydrous dichloromethane (80 mL) was added triethylamine (16.3 mL, 116.9 mmol) at 0 C under argon atmosphere, followed by 4-methylbenzenesulfonyl chloride (9.62 g, 50.6 mmol) and 4-dimethylaminopyridine (436 mg, 3.9 mmol). The reaction mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with dichloromethane (80 mL), and organic layer was washed with 2 M HCl (90 mL), saturated aqueous sodium bicarbonate solution (80 mL), and brine (80 mL). The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated to give (1-(trifluoromethyl)cyclopropyl)methyl 4-methylbenzenesulfonate as a light yellow oil (7.30 g, 64% over two steps). LCMS: LC retention time 2.08 min. MS (ESI) m/z 295 [M+H]+. 1H NMR (400 MHz, chloroform-d) δ 7.79 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 4.10 (s, 2H), 2.46 (s, 3H), 1.12 (m, 2H), 0.84 (m, 2H) ppm.

  • 3
  • [ 277756-46-4 ]
  • [ 371917-17-8 ]
YieldReaction ConditionsOperation in experiment
95% With borane-THF; In tetrahydrofuran; at 40℃; for 12h;Inert atmosphere; [01041]A mixture of 1-(trifluoromethyl)cyclopropane-1-carboxylic acid (3.0 g, 19.47 mmol, 1.00 equiv), tetrahydrofuran (30 mL), BH3.THF (31.2 mL, 1M in THF, 1.60 equiv) was stirred for 12 h at 40C under nitrogen. The reaction was quenched by saturated NH4C1 and the solid was filtered out. The liquid was extracted with ethyl acetate, washed with saturated solution of sodium bicarbonate and brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in the title compound (2.6 g, 95%) as colorless oil. GCMS [mlz] 140.
91.7% With borane-THF; at 40℃; A solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (6.0 g, 38.9 mmol) in BH3-THF (70 mL) was stirred at 40 C overnight. The mixture was quenched with saturated NH4Cl and extracted with EA (200 mL x 3). The organics were washed with saturated NaHCO3aqueous solution, brine, dried over Na2SO4, filtered and concentrated to afford (1- (trifluoromethyl)cyclopropyl)methanol as a colorless oil (5.0 g, 91.7%).1H NMR (400 MHz, DMSO-d6) d 4.93 (t, J = 6.0 Hz, 1H), 3.52 (d, J = 6.0 Hz, 2H), 0.86-0.75 (m, 4H).
90% With borane-THF; In tetrahydrofuran; at 40℃; Example B2 A solution of 1-(trifluoromethyl)cyclopropane-1-carboxylic acid (3 g, 19.47 mmol) in THF (32.4 mL) was treated with borane-THF complex (1.0 M, 31.2 mL, 31.2 mmol) and heated at 40 C. overnight. The mixture was cooled in an ice bath, carefully quenched with satd. NH4Cl, filtered through diatomaceous earth and rinsed well with EtOAc. The filtrate was extracted with EtOAc (2×) and the combined organics were washed with satd. NaHCO3, then brine, dried over Na2SO4 and concentrated to afford (1-(trifluoromethyl)cyclopropyl)methanol (2.46 g, 90%). 1H NMR (400 MHz, DMSO-d6): δ 4.93 (t, J=6.0 Hz, 1H), 3.52 (d, J=6.0 Hz, 2H), 0.86-0.75 (m, 4H).
86% With lithium aluminium hydride; In diethyl ether; at 0 - 20℃;Inert atmosphere; Treat a 0C solution of l-(trifluoromethyl)cyclopropanecarboxylic acid (9 g, 58.4 mmol) in ether (140 mL), under N2, portion-wise with LAH (2.9 g, 76 mmol), allow to warm to RT and stir overnight. Re-cool to 0C, slowly add HC1, warm to RT and separate the layers. Extract the aqueous layer with ether (2x), wash the combined organics with brine, dry over Na2S04 and concentrate under reduced pressure (water bath temp <30C) to afford the title compound (7 g, 86%). 1HNMR (400 MHz, DMSO-d6): δ 4.94 (t, J = 6.0 Hz, 1 H), 3.54 (d, J = 6.0 Hz, 2 H), 0.87-0.84 (m, 2 H), 0.81-0.79 (m, 2 H).
77% Step 1: 50 mL of borane dimethylsulfide 2M in THF were added dropwise at RT via an addition funnel to a solution of 1-trifluormethyl-cyclopropanecarboxylic acid (10 g, 64.90 mmol) in 100 mL of THF. The resulting clear solution was stirred at 40 C. for 24 hours before being cooled to 0 C. and quenched by slow addition of aqueous saturated NH4Cl. The biphasic slurry was filtered through celite. The organic layer was separated, and the aqueous layer was back extracted twice with AcOEt. The combined organic layers were dried (Na2SO4), filtered, and evaporated to give 7 g of (1-trifluoromethyl-cyclopropyl)-methanol (77% yield). Used as in the next step.
77% A mixture of 1-(trifluoromethyl)cyclopropane-1-carboxylic acid (0.50 g, 3.25 mmol) BH3 (1 N in THF, 5 mL) was refluxed for 1 hr and cooled to room temperature. 1 mL 12 N aqueous HCl was added. The reaction mixture was stirred for another 10 min. The solvent was removed under reduced pressure. The residue was partitioned between Et2O (20 mL) and water (20 mL). The organic layer was separated. The aqueous layer was extracted with Et2O (2 x 20 mL). The combined organic layer was washed with brine (2 x 50 mL), dried over anhydrous Na2SO4and evaporated to give the product as a colorless oil (0.35 g, yield: 77%).
70% With lithium aluminium hydride; In diethyl ether; at 0 - 20℃; l-(Trifluoromethyl)cyclopropane-l-carboxylic acid (858 mg, 5.57 mmol, 1.00 eq.) was dissolved in diethyl ether (15 mL). The reaction mixture was cooled to 0 C. Lithium aluminum hydride (274 mg, 7.24 mmol, 1.30 eq.) was added portionwise. The reaction mixture was stirred overnight and allowed to reach room temperature. The reaction mixture was cooled to 0 C. HC1 (aq., 1 N, 25 mL) was added dropwise. The aqueous phase was extracted with diethyl ether (2 χ 25 mL). The combined organic phases were washed with brine (25 mL), dried over sodium sulfate, filtered and evaporated in vacuo (Tbath < 30 C) to give (l-(trifluoromethyl)cyclopropyl)methanol (547 mg, 3.90 mmol, 70% yield) as a colorless oil. 1H NMR (CDC13): d 3.73 (s, 2H), 1.58 (br, 1H), 1.07-1.01 (rn 2H), 0.82-0.75 (m, 2H).
45% With lithium aluminium hydride; In diethyl ether; at 0℃; for 2h;Inert atmosphere; Lithium aluminum hydride (183mg, 4.8mmol) was dissolved in anhydrous diethyl ether (10 mL), and replaced with nitrogen. Was cooled to 0 deg. C, was slowly added ether solution of 1-trifluoromethyl-1-cyclobutane carboxylic acid. At this temperature the reaction 2 hours, 0.5ml of saturated sodium sulfate solution was added, inorganics filtered, dried, and concentrated to give [1-(trifluoromethyl)cyclopropyl]methanol (pale yellow liquid, 250mg), 45% yield.
45.3% With lithium aluminium hydride; In tetrahydrofuran; at 0 - 40℃; Step 1 1-(Trifluoromethyl)cyclopropane-1-carboxylic acid (XXV) (3.7334 g, 24.23 mmol) was dissolved in THF (162 mL) and cooled to 0 C. LAH (1.1614 g, 29.07 mmol) was then added and the reaction heated to 40 C. overnight. The reaction was cooled to 0 C. Water (2 mL) was added to quench the reaction followed by 2 N NaOH (0.3 mL). The reaction was stirred forming a precipitate which was filtered off and washed with ether. The aqueous phase was removed and the organic phase was washed with brine, dried, and carefully concentrated to give (1-(trifluoromethyl)cyclopropyl)methanol (XXVI) (1.5376 g, 10.98 mmol, 45.3% yield) as a clear, volatile liquid.
45.3% With lithium aluminium hydride; In tetrahydrofuran; at 0 - 40℃; 1-(Trifluoromethyl)cyclopropane-1-carboxylic acid (LVIII) (3.7334 g, 24.23 mmol) was dissolved in THF (162 mL) and cooled to 0 C. LAH (1.1614 g, 29.07 mmol) was then added and the reaction heated to 40 C. overnight. The reaction was cooled to 0 C. Water (2 mL) was added to quench the reaction followed by 2 N NaOH (0.3 mL). The reaction was stirred forming a precipitate which was filtered off and washed with ether. The aqueous phase was removed, and the organic phase was washed with brine, dried, and carefully concentrated to give (1-(trifluoromethyl)cyclopropyl)methanol (LIX) (1.5376 g, 10.98 mmol, 45.3% yield) as a clear, volatile liquid.
28.6% With lithium aluminium hydride; In tetrahydrofuran; at 20℃; A 2M solution of lithium aluminum hydride in THF (2.11 mL, 4.22 mmol) was added dropwise to a solution of 1-(trifluoromethyl)-1-cyclopropanecarboxylic acid (500.0 mg, 3.24 mmol) in THF (8 mL) cooled to 0C The reaction mixture was stirred at room temperature overnight then was quenched with sodium sulfate decahydrate. The resulting suspension was filtered and the filtrate was evaporated in vacuo to give [1- (trifluoromethyl)cyclopropyl]methanol (130 mg, 0.928 mmol, 28.6% yield) as a colourless oil.1H NMR (400 MHz, DMSO-d6) δ 0.75 - 0.92 (m, 4H), 3.55 (d, J = 5.91 Hz, 2H), 4.93 (t, J = 6.00 Hz, 1H).
28.6% With lithium aluminium hydride; In tetrahydrofuran; at 20℃; A 2M solution of lithium aluminum hydride in THF (2.11 mL, 4.22 mmol) was added dropwise to a solution of 1-(trifluoromethyl)-1-cyclopropanecarboxylic acid (500.0 mg, 3.24 mmol) in THF (8 mL) cooled to 0C The reaction mixture was stirred at room temperature overnight then was quenched with sodium sulfate decahydrate. The resulting suspension was filtered and the filtrate was evaporated in vacuo to give [1- (trifluoromethyl)cyclopropyl]methanol (130 mg, 0.928 mmol, 28.6% yield) as a colourless oil.1H NMR (400 MHz, DMSO-d6) δ 0.75 - 0.92 (m, 4H), 3.55 (d, J = 5.91 Hz, 2H), 4.93 (t, J = 6.00 Hz, 1H).
With lithium aluminium hydride; In diethyl ether; for 1h;Inert atmosphere; Step 1: Synthesis of (l-(trtfluoromethyl)cyclopropyl)methanol:To a stirred solution of Lithium aluminium hydride (2.4 g) in dry ether (70 ml) l-(trifluoromethyl)cyclopropanecarboxylic acid (5 g) was added at 0 C under N2 atmosphere and the reaction mixture was stirred for about 1 hour. After completion of the reaction (monitored by - NMR), the reaction mixture was quenched by cautious addition of water (1 ml), 15 % aq. NaOH solution (1 ml) and again water (3 ml) and stirred for 30 minutes. The reaction mixture was filtered and cake was washed with ether twice. Due to volatile nature of the compound, only half of the ether volume was reduced on hot water both using without any vacuum and next reaction was proceeded as such. 1H NMR (CDC13, 300 MHz): δ 3.73 (s, 2H), 1.83 (br s, 1H), 1.05- 1.01 (m, 2H), 0.80- 0.76 (m, 2H); ES Mass: (M- H) 138.91
To a solution of compound 1-trifluoromethyl-cyclopropanecarboxylic acid (2 g, 13 mmol) in dry THF (80 mL) was added LAH (592 mg, 16 mmol) in portions at 0 C. and the resulting mixture was heated at 40 C. overnight. H2O (592 mg, 16 mmol) was added to quench the reaction at 0 C. and followed by 2N NaOH (0.6 mL). After filtration, the filtrate was distilled to remove the most solvent to give crude (1-trifluoromethyl-cyclopropyl)-methanol (1.2 g crude), which was used in the next step without further purification.
With lithium aluminium hydride; In tetrahydrofuran; at 30℃; for 14h;Cooling with ice; Lithium aluminum hydride (approximately 78.45 g, 2.067 mol) (pellets) were added to the flask, THF (2.450 L) was added to the addition funnel, and the system was cycled 3 times with vacuum/ nitrogen. The solvent was quickly added to the LAH pellets, stirred at room temperature for 0.5 h (pellets start to fall apart to give a grey suspension), and cooled in an ice bath. A solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (245 g, 1.590 mol) in THF (735.0 mL) was slowly added via an addition funnel over 0.5-1 h, keeping the internal temperature below 30 C. The grey suspension was stirred in the melting ice bath for 14 hours. The grey suspension was quenched under ice cooling by slow addition of water (approximately 75.92 g, 75.92 mL, 4.214 mol), followed by NaOH (approximately 76.32 mL of 6 M, 457.9 mmol) and water(approximately 75.92 g, 75.92 mL, 4.214 mol). The grey suspension was stirred at ~50 C till the solid became colorless (~0.5 h), treated with magnesium sulfate (20 g), filtered over Celite, and the aluminium salts were washed with three portions of hot THF. The filtrate was dried again over magnesium sulfate, filtered, and concentrated by evaporation at 55 C and 450 mbar to give [1-(trifluoromethyl)cyclopropyl]methanol as a 62 wt% solution (NMR) in THF (327 g, 91%). 1H NMR (400 MHz, DMSO-d6) δ 4.94 (t, J = 6.0 Hz, 1H), 3.56 (d, J = 6.0 Hz, 2H), 0.91 - 0.74 (m, 4H)
With lithium aluminium hydride; In tetrahydrofuran; diethyl ether; at -15℃; for 0.5h; 1 M Lithium aluminium hydride in tetrahydrofuran (4.55ml, 4.55mmol) was slowly added to a stirred solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (1g, 6.5mmol) in diethyl ether (6ml) at -15C. The mixture was stirred for 30 minutes, warmed to room temperature, quenched with water and extracted with diethyl ether (x3). The combined organic phases were dried (MgS04) and concentrated to ~5ml.
With lithium aluminium hydride; In tetrahydrofuran; at 26℃; for 18h; To a round bottom flask were added 1- (trifluoromethyl) cyclopropanecarboxylic acid (5000 mg, 32.4 mmol) , THF (100 mL) and LiAlH4(1847 mg, 48.7 mmol) in portions at 0 . The reaction mixture was stirred for 18 h at 26 . The mixture was cooled to RT, quenched with 15NaOH solution (1.85 mL) and water (1.85 mL) . Anhydrous sodium sulfate was added and the mixture was stirred for 30 mins. The mixture was filtered and the filtrated was concentrated in vacuum to give the title compound.1H NMR (CDCl3, 400 MHz) : δ 4.92 (t, J 6.06 Hz, 1H) , 3.52 (d, J 5.87 Hz, 2H) , 0.80-0.86 (m, 2H) , 0.73-0.80 (m, 2H) .
5.11 g With dimethylsulfide borane complex; In tetrahydrofuran; at 40℃; for 18h;Inert atmosphere; To a stirred solution of 1-(trifluoromethyl)cyclopropane-1-carboxylic acid (6.0 g, 38.96 mmol) in anhydrous tetrahydrofuran (35 mL) was added borane-methyl sulfide complex (29.2 mL, 2.0 M solution in THF, 58.4 mmol) at room temperature under argon atmosphere. The resulting reaction mixture was stirred at 40 C for 18 h. The reaction was quenched by adding saturated aqueous ammonium chloride solution (120 mL). The resulting solid was filtered off. The filtrate was extracted with diethyl ether (50 mL × 3). The combined organic solution was washed with saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL). Then, the organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give (1-(trifluoromethyl)cyclopropyl)methanol as a light yellow oil (5.11 g). LCMS: MS (ESI) m/z was not observed. 1H NMR (400 MHz, chloroform-d) δ 3.73 (s, 2H), 1.05-1.02 (m, 2H), 0.78 (m, 2H) ppm.

  • 4
  • [ 208242-25-5 ]
  • [ 371917-17-8 ]
YieldReaction ConditionsOperation in experiment
64% With diisobutylaluminium hydride; In dichloromethane; at 0℃; for 2h; [1691] At oo C., 26.7 ml (26.7 mmol) of diisobutylaluminumhydride (1M in dichloromethane) were slowly addeddropwise to a solution of 1.89 g (10.7 mmol) of methyl1-(trifluoromethyl)cyclopropanecarboxylate in 10 ml ofdichloromethane. The mixture was then stirred at oo C. foranother 2 hand the reaction was subsequently terminated byaddition of 10 ml of methanol. The reaction mixture wasdiluted with 30 ml of aqueous 20% strength sodium potassiumtartrate solution and 30 ml of aqueous buffer solution(pH 7) and stirred vigorously at room temperature overnight.The phases were separated and the aqueous phase wasextracted three times with dichloromethane. The combinedorganic phases were dried over magnesium sulphate and filtered,and the solvent was removed under reduced pressure.The crude product corresponded to the title compound. Yield:0.96 g (64% of theory)[1692] 1H-NMR (400 MHz, CDCI3 ): ll [ppm]=3.74 (d,2H), 1.65 (t, lH), 1.06-1.02 (m, 2H), 0.81-0.76 (m, 2H).
EXAMPLE 11; 1-(Methylsulfonyl)-4-(4-(1-(1-((1-(trifluoromethyl)cyclopropyl)methyl)piperidin-4-yl)ethoxy)phenyl)-1,2,3,6-tetrahydropyridine 1. (1-(Trifluoromethyl)cyclopropyl)methanolTo an ice-cold suspension of lithium aluminum hydride (33.91 mmoles; 1.29 g) in diethyl ether (90 mL) is added dropwise over 25 minutes methyl 1-(trifluoromethyl)cyclopropanecarboxylate (16.95 mmoles; 3.00 g) in 30 mL of diethylether. The reaction is stirred at 0 C. for 2 hours. The mixture is quenched by slow addition of 7.5 mL of water, then 15 mL of 5 M sodium hydroxide and 9 mL of water. The thick slurry is vigourously stirred at room temperature for 3 hours. The mixture is transferred to a separatory funnel, diluted with water and extracted with diethylether. The combined organic layers are washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness. 2.37 g of the title compound as a colorless oil are obtained. 2.37 g. 1H NMR (CDCl3) d (ppm): 0.762-0.807 (m, 2H), 1.018-1.055 (m, 2H), 3.732 (s, 2H).
0.96 g With diisobutylaluminium hydride; In methanol; dichloromethane; at 0℃; for 2h; At 0 C, 26.7 ml (26.7 mmol)of diisobutylaluminium hydride (1M in dichloromethane) were slowly addeddropwise to a solution of 1.89 g (10.7 mmol) of methyl1-(trifluoromethyl)cyclopropanecarboxylate in 10 ml of dichloromethane. Themixture was then stirred at 0 C for another 2 h and the reaction wassubsequently terminated by addition of 10 ml of methanol. The reaction mixturewas diluted with 30 ml of aqueous 20% strength sodium potassium tartratesolution and 30 ml of aqueous buffer solution (pH 7) and stirred vigorously atroom temperature overnight. The phases were separated and the aqueous phase wasextracted three times with dichloromethane. The combined organic phases weredried over magnesium sulphate and filtered, and the solvent was removed underreduced pressure. The crude product corresponded to the title compound. Yield:0.96 g (64% of theory)
  • 5
  • [ 371917-17-8 ]
  • [ 1360569-32-9 ]
  • 6
  • [ 371917-17-8 ]
  • [ 1360569-39-6 ]
  • 7
  • [ 371917-17-8 ]
  • [ 1360569-40-9 ]
  • 8
  • [ 371917-17-8 ]
  • [ 1360569-45-4 ]
  • 9
  • [ 371917-17-8 ]
  • [ 1360569-46-5 ]
  • 10
  • [ 371917-17-8 ]
  • [ 1360569-00-1 ]
  • 11
  • [ 371917-17-8 ]
  • [ 1360569-01-2 ]
  • 12
  • [ 371917-17-8 ]
  • [ 1360569-02-3 ]
  • 13
  • [ 371917-17-8 ]
  • [ 1360569-09-0 ]
  • 14
  • [ 371917-17-8 ]
  • [ 1360569-10-3 ]
  • 15
  • [ 371917-17-8 ]
  • [ 1360569-11-4 ]
  • 17
  • [ 371917-17-8 ]
  • [ 1155272-93-7 ]
YieldReaction ConditionsOperation in experiment
To a solution of (1-trifluoromethyl-cyclopropyl)-methanol (1.2 g, 8.57 mmol) and Et3N (1.04 g, 10.28 mmol) in dry DMF (10 mL) at -10 C. was added methanesulfonyl chloride (981 mg, 8.57 mmol) over 20 minutes, while retaining the inner temperature at 0 C. After the addition was complete, the resulting solution was stirred at 0 C. for 30 minutes, the resulting mixture was filtered and washed with DMF (3 mL). To the combined filtrates was added sodium bromide (3.7 g, 36 mmol) and the resulting mixture was stirred at room temperature overnight. The mixture was cooled in ice, followed by addition of pentane (20 mL) and water (15 mL) while retaining the mixture at 0 C., prior to liquid separation. The organic phase was dried over Na2SO4 and filtered. The filtrate was distilled to remove the most of pentane to give 1-bromomethyl-1-trifluoromethyl-cyclopropane (0.9 g crude), which was used without further purification.
  • 18
  • [ 371917-17-8 ]
  • diisopropyl 2-((1-(trifluoromethyl)cyclopropyl) methyl)malonate [ No CAS ]
  • 19
  • [ 371917-17-8 ]
  • 2-((1-(trifluoromethyl)cyclopropyl)methyl)malonic acid [ No CAS ]
  • 20
  • [ 371917-17-8 ]
  • 3-(1-(trifluoromethyl)cyclopropyl)propanoic acid [ No CAS ]
  • 21
  • [ 371917-17-8 ]
  • 3-(1-(trifluoromethyl)cyclopropyl)propanamide [ No CAS ]
  • 22
  • [ 371917-17-8 ]
  • N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide [ No CAS ]
  • 23
  • [ 371917-17-8 ]
  • N-((6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide [ No CAS ]
  • 24
  • [ 371917-17-8 ]
  • C7H8ClF3O [ No CAS ]
  • 25
  • (S)-N-((6-amino-4-((4-fluorophenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide hydrochloride [ No CAS ]
  • [ 530-62-1 ]
  • [ 371917-17-8 ]
  • (S)-(1-(trifluoromethyl)cyclopropyl)methyl (2-(acetamidomethyl)-4-((4-fluorophenyl)sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 24 ~ Synthesis of (S)-(l-(trifluoromethyl)cyclopropyl)methyl (2- (acetamidomethyl)-4-((4-fluorophenyl)sulfonyl)-3,4-dihydro-2H-benzo[6] [l,4]oxazin-6- yl)carbamate (24) [0312] A solution of (S)-N-((6-amino-4-((4-fluorophenyl)sulfonyl)-3 ,4-dihydro-2H- benzo[][l,4]oxazin-2-yl)methyl)acetamide hydrochloride (30 mg, 0.072 mmol), carbonyldiimidazole (46.8 mg, 0.289 mmol), and N,N-dimethylpyridin-4-amine (1.50 mg, 0.012 mmol) in acetonitrile (500 μ) was sealed and heated at 80 C. After twenty-two hours, a solution of (l-(trifluoromethyl)cyclopropyl)methanol (152 mg, 1.08 mmol) in acetonitrile (500 μ) was added to the reaction. The mixture was heated at 80 C for forty five minutes. The mixture was cooled, and concentrated. The residue was dissolved in DMSO (1 mL), filtered, and purified via reverse-phase HPLC (MeCN: water, trifluoroacetic acid buffer) to afford ( )-(l- (trifluoromethyl)cyclopropyl)methyl (2-(acetamidomethyl)-4-((4-fluorophenyl)sulfonyl)-3,4- dihydro-2H-benzo[6][l,4]oxazin-6-yl)carbamate. LRMS (ESI) calculated for C23H23F4N3O6S (M+H)+: 546, Found: 546. 1H NMR (600 MHz, DMSO- 6) δ 9.71 (s, 1H), 8.06 (1H, t, J= 5.5 Hz), 7.96 (s, 1H), 7.73 (1H, dd, J= 8.7 Hz, 3.8 Hz), 7.41 (2H, t, J= 10.2 Hz), 7.16 (1H, d, J = 9.3 Hz), 6.76 (1H, d, J= 9.2 Hz), 4.24 (m, 3H), 3.26 (m, 2H), 3.18 (m, 1H), 3.08 (m, 1H), 1.83 (s, 3H), 1.03 (m, 4H).
  • 26
  • [ 358-23-6 ]
  • [ 371917-17-8 ]
  • [ 1415818-45-9 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at -78℃; for 0.5h; [1694] At -78 C., a solution of 428 mg (3.06 mmol) of[1-(trifluoromethyl)cyclopropyl]methanol and 468 fll (3.36mmol) of triethylamine in 1.5 ml of dichloromethane wasadded dropwise to 569 fll (3.36 mmol) oftrifluoromethanesulphonicanhydride in 1.5 ml of dichloromethane such thatthe internal temperature did not exceed -50 C. The mixturewas stirred at -78 C. for another 30 min and spontaneouslywarmed toRT. The reaction mixture was diluted with 25 ml ofmethyl tert-butyl ether, washed three times with 20 ml of amixture of saturated aqueous sodium chloride solution/INhydrochloric acid (3:1), dried over magnesium sulphate, filteredand concentrated at 25 C. and a pressure of 2:100 mbar.The crude product was used for the next step without furtherpurification. Yield: 701 mg (84% of theory)
701 mg With triethylamine; In dichloromethane; at -78 - 20℃; for 0.5h; At -78 C, a solution of 428mg (3.06 mmol) of [1-(trifluoromethyl)cyclopropyl]methanol and 468 [11 (3.36mmol) of triethylamine in 1.5 ml of dichloromethane was added dropwise to 5691,11 (3.36 mmol) of trifluoromethanesulphonic anhydride in 1.5 ml ofdichloromethane such that the internal temperature did not exceed -50 C. Themixture was stirred at -78 C for another 30 min and spontaneously warmed to RT.The reaction mixture was diluted with 25 ml of methyl tert-butyl ether, washedthree times with 20 ml of a mixture of saturated aqueous sodium chloridesolution/1N hydrochloric acid (3:1), dried over magnesium sulphate, filteredand concentrated at C and a pressure of >100 mbar. The crude product wasused for the next step without further t 'nu r ()feign l_AiLLIJI.:JeS purification. Yield: 701 mg (84% of theory)
  • 27
  • [ 371917-17-8 ]
  • 2-[1-(trifluoromethyl)cyclopropyl]acetic acid [ No CAS ]
  • 28
  • [ 371917-17-8 ]
  • 2-[1-(trifluoromethyl)cyclopropyl]ethan-1-ol [ No CAS ]
  • 29
  • [ 371917-17-8 ]
  • 2-[(2-chloro-6-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrimidin-4-yl)methyl]-2,3-dihydro-1H-isoindole-1,3-dione [ No CAS ]
  • 30
  • [ 371917-17-8 ]
  • 2-[(2-cyclopropyl-6-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrimidin-4-yl)methyl]-2,3-dihydro-1H-isoindole-1,3-dione [ No CAS ]
  • 31
  • [ 371917-17-8 ]
  • (2-cyclopropyl-6-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrimidin4-yl)methanamine [ No CAS ]
  • 32
  • [ 716358-53-1 ]
  • [ 371917-17-8 ]
  • 5-(N-methylsulfamoyl)-2-(1-(trifluoromethyl)cyclopropyl)methoxybenzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% Take 50mL single-mouthed flask, was added 121mg <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> and 2mL DMF, cooled to 0 deg. C, was added 61mgNaH, stirred for 30 minutes, was added 200mg 2-fluoro-5-(N-methylsulfamoyl)benzoic acid, stirred at room temperature overnight, concentrated hydrochloric acid to adjust pH to about 2, large amount of solid precipitated, filtered, and dried in vacuo to give a white solid 110mg, yield: 36%.
  • 33
  • [ 247569-56-8 ]
  • [ 371917-17-8 ]
  • 5-methylsulfonyl-2-(1-(trifluoromethyl)cyclopropyl)methoxybenzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.8% To a 100mL round-bottomed flask was added <strong>[371917-17-8](1-(trifluoromethyl)cyclopropyl)methanol</strong> (168.1mg, 1.2mmol), DMF (5mL) and THF (5mL), N2 protection, was added sodium tert-butoxide (288.3mg , 3mmol), was added after stirring for 30 minutes 2-fluoro-5-(methylsulfonyl)benzoic acid (218mg, 1.0mmol), stirred overnight. Was added 40mL of water, PH adjusted to 1.5 with dilute hydrochloric acid and the precipitated solid was filtered, the filter cake was dissolved in dichloromethane and the solution dried over anhydrous sodium sulfate, and concentrated to give 263mg, yield: 77.8%.
  • 34
  • [ 371917-17-8 ]
  • 3-(4-(4-cyano-2-fluorophenyl)piperazine-1-carbonyl)-N-methyl-4-(1-(trifluoromethyl)cyclopropyl)methoxybenzenesulfonamide [ No CAS ]
  • 35
  • [ 371917-17-8 ]
  • {4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}[5-methylsulfonyl-2-[1-(trifluoromethyl)cyclopropyl]methoxy}phenyl]methanone [ No CAS ]
  • 36
  • [ 371917-17-8 ]
  • 4-(4-(5-methylsulfonyl-2-(1-(trifluoromethyl)cyclopropyl)methoxybenzoyl)piperazin-1-yl)benzonitrile [ No CAS ]
 

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