Tetrahydrofuran → Biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

HRID 2113261Notes

Reaction equation

HRID 2113261 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.[C:12]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][C:19]([O:21][CH:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][C:30]([NH:32][C:33]2[C:42]([CH3:43])=[CH:41][C:36]([C:37](OC)=[O:38])=[C:35]([CH3:44])[CH:34]=2)=[O:31])[CH2:24][CH2:23]1)=[O:20].[OH-].[Na+]>ClCCl.O>[OH:38][CH2:37][C:36]1[C:35]([CH3:44])=[CH:34][C:33]([NH:32][C:30]([CH2:29][CH2:28][N:25]2[CH2:24][CH2:23][CH:22]([O:21][C:19](=[O:20])[NH:18][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH2:27][CH2:26]2)=[O:31])=[C:42]([CH3:43])[CH:41]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 46239621Methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoate

Product 1

HCID 46239523Biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1M lithium aluminum hydride in THF (1.52 mL, 1.52 mmol) at 0° C. was added methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoate (400 mg, 0.76 mmol). The resulting mixture was stirred at 0° C. for 30 minutes and then a 1:1 mixture of 1M aqueous sodium hydroxide (5 mL) and water (5 mL) was added and stirring was continued for 2 hours. Dichloromethane was added and the organic layer was separated, dried over sodium sulfate and the solvent removed under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane containing 5% methanol to provide biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)-ethyl]piperidin-4-yl ester. LCMS (10-70) Rt=3.94; [M+H+] found 502.5.

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued for 2 hours
  4. customthe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with dichloromethane containing 5% methanol

Sources & evidence

ORD record
ord-4e67d5465bbc4476bdff74c173899c31
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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