Sodium hydride → 4-{[4-(4-Fluorobenzyloxy)-phenyl]-(3-methyl-butyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1069460Notes

Reaction equation

HRID 1069460 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].CS(O[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)(=O)=O>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)=[CH:22][CH:21]=2)[CH2:15][CH2:16][CH:17]([CH3:18])[CH3:19])[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 18380576Benzenemethanol, 4-fluoro-, 1-methanesulfonateHCID 542988674-[(4-Hydroxy-phenyl)-(3-methyl-butyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 544663194-{[4-(4-Fluorobenzyloxy)-phenyl]-(3-methyl-butyl)-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-[(4-hydroxy-phenyl)-(3-methyl-butyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (In, 1.18 g, 3.26 mmol) was dissolved in DMF (7 mL), treated with NaH (0.26 g, 6.52 mmol, 60% dispersion in mineral oil), and stirred for 8 minutes. 4-Fluorobenzyl methanesulfonate (Ie, 0.93 g, 4.56 mmol) was added and the reaction was stirred for 5 minutes, then diluted with EtOAc (100 mL), washed with saturated sodium bicarbonate solution and with brine, dried over Na2SO4, and concentrated. The residue was chromatographed on silica gel eluting with 4:1 hexane/EtOAc to give 1.39 g (91%) of the desired product.

Workup

  1. stirringthe reaction was stirred for 5 minutes
  2. washwashed with saturated sodium bicarbonate solution and with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel eluting with 4:1 hexane/EtOAc

Sources & evidence

ORD record
ord-a5ee76c4ed3444c8b1fae5621180f13f
Source dataset
uspto-grants-2001_06
Patent number
US06251918B1

Reaction notes

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