Water → Benzyl [4-(3-hydroxy-1-methylpiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamate

HRID 518807Notes

Reaction equation

HRID 518807 reaction equation
[BH4-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[C:12]([O:27][CH:28]([CH3:30])[CH3:29])[CH:11]=2)[C:6](=[O:31])[CH2:5]1.O.[Cl-].[Na+]>C(O)C.C(OCC)(=O)C>[OH:31][CH:6]1[CH:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[C:12]([O:27][CH:28]([CH3:29])[CH3:30])[CH:11]=2)[CH2:8][CH2:9][N:4]([CH3:3])[CH2:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 5234Sodium ChlorideHCID 4311764Sodium borohydrideHCID 86697978Benzyl [4-(1-methyl-3-oxopiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamate

Product 1

HCID 86697979Benzyl [4-(3-hydroxy-1-methylpiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamateYield 26%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

486 mg of NaBH4 are added, in portions, to a suspension of 700 mg of benzyl [4-(1-methyl-3-oxopiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamate in 35 ml of ethanol brought to 5° C. The reaction medium is stirred at ambient temperature for 50 minutes. 4 ml of water, 15 ml of a saturated aqueous sodium chloride solution and 40 ml of ethyl acetate are added. The two phases are separated, and the aqueous phase is washed with twice 20 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and evaporated. Purification is carried out by flash chromatography on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and (MeOH+10% NH4OH) (99/1 to 90/10). 183 mg of benzyl [4-(3-hydroxy-1-methylpiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamate (trans diastereoisomers) and 183 mg of benzyl [4-(3-hydroxy-1-methylpiperidin-4-yl)-2-(propan-2-yloxy)phenyl]carbamate (cis diastereoisomers) are obtained.

Workup

  1. custombrought to 5° C
  2. customThe two phases are separated
  3. washthe aqueous phase is washed with twice 20 ml of ethyl acetate
  4. dry with materialThe combined organic phases are dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification
  8. washis carried out by flash chromatography on silica gel (40-63 μm), elution
  9. additionbeing carried out with a mixture of dichloromethane and (MeOH+10% NH4OH) (99/1 to 90/10)

Sources & evidence

ORD record
ord-fb9b42a93e94437c9ac4aa2a8d3da8a8
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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