Acetic Acid → HCID 68427101, compound

HRID 1442659Notes

Reaction equation

HRID 1442659 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.[O:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C1COCC1.CCOC(C)=O>[CH:1]1([N:4]([CH:20]2[CH2:21][CH2:22][N:23]([CH:29]3[CH2:30][CH2:31][O:26][CH2:27][CH2:28]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 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59031023HCID 59031023, compound

Product 1

HCID 68427101HCID 68427101, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21493386Dce thfSolvent

Conditions

Temperature
75 °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 (73 mg, 0.20 mmol, 1.0 equiv.), tetrahydro-4H-pyran-4-one (65 μL, 7.0 mmol, 3.5 equiv.) and AcOH (23 μL, 0.40 mmol, 2 equiv.) in 1,2-dichloroethane/THF (2/1, 1.5 mL) was treated with NaBH(OAc)3 (210 mg, 1.00 mmol, 5.0 equiv.). After being stirred for 48 h at 75° C., 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, 0-10% MeOH/CH2Cl2, gradient elution) gave the title compound as a white solid: 1H NMR (CDCl3, 500 MHz) δ 7.58 (d, J=8.3 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 4.26-4.20 (m, 1H), 4.06-4.02 (m, 2H), 3.40-3.35 (m, 2H), 3.14-3.07 (m, 2H), 2.55-2.52 (m, 2H), 2.48 (s, br, 1H), 2.39-2.35 (m, 2H), 2.16-2.07 (m, 2H), 1.99-1.93 (m, 2H), 1.79 (s, 3H), 1.80-1.73 (m, 2H), 1.65-1.60 (m, 2H), 0.58-0.53 (m, 2H), 0.47-0.42 (m, 2H); MS(ESI) 441 [M+H]+.

Workup

  1. washwashed (1×1 N aqueous NaOH, and 1× brine)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification of the residue
  5. washby flash chromatography (SiO2, 0-10% MeOH/CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-1fbb470c3cee4a7bafe27de1825a3034
Source dataset
uspto-grants-2010_02
Patent number
US07659287B2

Reaction notes

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