Acetic Acid → HCID 59031029, compound

HRID 1442658Notes

Reaction equation

HRID 1442658 reaction equation
[CH:1]1([N:4]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.C(O[C:29]1(O[Si](C)(C)C)[CH2:31][CH2:30]1)C.CC(O)=O.[BH3-]C#N.[Na+]>CO.CCOC(C)=O>[CH:1]1([N:4]([CH:20]2[CH2:21][CH2:22][N:23]([CH:29]3[CH2:31][CH2:30]3)[CH2:24][CH2:25]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 59031023HCID 59031023, compound

Product 1

HCID 59031029HCID 59031029, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-N-cyclopropyl-N-(piperidin-4-yl)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzamide prepared above in step c in Example 1 (120 mg, 0.337 mmol, 1.0 equiv.), (1-ethoxycyclopropoxy)trimethylsilane (404 μL, 2.02 mmol, 6.0 equiv.) and AcOH (193 μL, 3.37 mmol, 10 equiv.) in MeOH (2.0 mL) was treated with NaBH3CN (95 mg, 1.52 mmol, 4.5 equiv.). After being stirred for 48 h at 25° C. and being refluxed for additional 24 h, the reaction was diluted (EtOAc) and washed (1×1 N aqueous NaOH, and 1× brine). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by flash chromatography (SiO2, 0-7% MeOH/CH2Cl2, gradient elution) gave the title compound as a pale yellow solid: 1H NMR (CDCl3, 500 MHz) δ 7.55 (d, J=8.2 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H), 4.22-4.13 (m, 1H), 3.12 (d, J=11.5 Hz, 2H), 2.96 (s, br, 1H), 2.54-2.50 (m, 1H), 2.39-2.22 (m, 2H), 2.12-1.99 (m, 2H), 1.88-1.82 (m, 2H), 1.74 (s, 3H), 1.61-1.57 (m, 1H), 0.88-0.85 (m, 2H), 0.55-0.41 (m, 6H); MS(ESI) 398 [M+H]+.

Workup

  1. temperaturebeing refluxed for additional 24 h
  2. washwashed (1×1 N aqueous NaOH, and 1× brine)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue
  6. washby flash chromatography (SiO2, 0-7% MeOH/CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-e3c470bab5c74424817cf7a636cc838a
Source dataset
uspto-grants-2010_02
Patent number
US07659287B2

Reaction notes

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