Sodium triacetoxyborohydride → HCID 11260625, compound

HRID 2103382Notes

Reaction equation

HRID 2103382 reaction equation
[NH2:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:22])[CH2:8][NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C@H:4]([CH3:23])[CH2:3]1.[OH:24][C:25]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CC(O)C>[OH:24][C:25]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:30][CH2:29][CH:28]([NH:1][C@@H:2]2[CH2:6][N:5]([C:7](=[O:22])[CH2:8][NH:9][C:10](=[O:21])[C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=3)[C@H:4]([CH3:23])[CH2:3]2)[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 211876304-Hydroxy-4-(pyridin-2-yl)cyclohexanoneHCID 57803416HCID 57803416, compound

Product 1

HCID 11260625HCID 11260625, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-{2-[(2R,4S)-4-Amino-2-methylpyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide (200 mg, 0.607 mmol) and 4-hydroxy-4-pyridin-2-yl-cyclohexanone (116 mg, 0.607 mmol) were dissolved in 2-propanol (10 mL). After stirring for 30 minutes, sodium triacetoxyborohydride (257 mg, 1.21 mmol) was added and the mixture was stirred at room temperature overnight. TLC indicated complete conversion to desired products in about a 1:1 ratio of two isomers. The reaction mixture was chromatographed on silica gel eluting with dichloromethane to 10% methanol/dichloromethane/0.5% ammonium hydroxide to give 229 mg (75%) as a mixture of isomers. 1H NMR (CDCl3, mixture of isomers) δ 8.53 (m, 1H), 8.13 (bs, 1H), 8.02 (d, 1H), 7.75 (m, 2H), 7.58 (t, 1H), 7.40 (m, 2H), 7.22 (m, 1H), 4.05-4.38 (m, 3H), 3.80 (m, 1H), 3.56 (m, 1H), 3.42 (m, 1H), 3.19 (m, 1H), 3.04 (m, 1H), 2.65 (m, 1H), 2.47 (m, 1H), 2.16 (m, 2H), 1.40-2.00 (m, 7H), 1.43 (d, 3H). LCMS (M+H)+: Higher Rf isomer m/z=505.2; Lower Rf isomer m/z=505.2.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe reaction mixture was chromatographed on silica gel eluting with dichloromethane to 10% methanol/dichloromethane/0.5% ammonium hydroxide
  3. customto give 229 mg (75%)
  4. additionas a mixture of isomers

Sources & evidence

ORD record
ord-f61e400a95b94d68b68cefe5fecb074f
Source dataset
uspto-grants-2009_08
Patent number
US07576089B2

Reaction notes

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