Ethanol → 3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamide

HRID 546138Notes

Reaction equation

HRID 546138 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:33])[C@@H:16]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C.C(O)C>Cl.C(OCC)(=O)C>[CH:18]1([CH2:17][C@H:16]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:32])[F:30])[CH:24]=2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:33])[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 2

HCID 702EthanolHCID 67189363N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2(R)-(3-trifluoromethyl-phenyl)-propionamide

Product 1

HCID 671910643-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamideYield 51%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In a flask containing N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2(R)-(3-trifluoromethyl-phenyl)-propionamide (66 mg, 0.13 mmol) was added ethanol (3 mL) and concentrated hydrochloric acid (three drops) and was stirred at 25° C. for 2 h. It was then diluted with ethyl acetate (30 mL) and washed with water (1×10 mL) and saturated aqueous brine solution (1×10 mL). The organic layer was then dried over sodium sulfate and absorbed onto silica gel (2 g) and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamide (26 mg, 51%) as a colorless gum: [α]26589=−22.5° (c=0.16, methanol); ES-HRMS m/e calcd for C20H24N3O2F3 (M+H)+ 396.1894, observed 396.1892; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.20 (m, 2H, CH2), 1.35-1.80 (m, 8H, 4×CH2), 2.07-2.19 (m, 1H, CH), 3.67 (q, J=5.6 Hz, 2H, OCH2), 3.89 (dd, J=9.0, 5.5 Hz, 1H, ArCH), 3.99 (t, J=5.6 Hz, 2H, NCH2), 4.83 (t, J=5.6 Hz, 1H, OH), 6.42 (d, J=2.2 Hz, 1H, Ar), 7.53 (d, J=2.2 Hz, 1H, Ar), 7.54-7.73 (m, 4H, Ar), 10.74 (s, 1H, NH).

Workup

  1. washwashed with water (1×10 mL) and saturated aqueous brine solution (1×10 mL)
  2. dry with materialThe organic layer was then dried over sodium sulfate
  3. customabsorbed onto silica gel (2 g)
  4. custompurified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bba769bd56c34b4fb6d5a06087ed25b9
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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