2,2-Difluoroethyl (4-methylphenyl)sulphonate → tert-Butyl 3-(2,2-difluoroethoxy)-4,4-dimethoxypiperidine-1-carboxylate

HRID 43688Notes

Reaction equation

HRID 43688 reaction equation
[OH:1][CH:2]1[C:7]([O:10][CH3:11])([O:8][CH3:9])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1.ClC1N=C(C(N[C@H]2CCN(C(OC(C)(C)C)=O)C[C@H]2OC)=O)NC=1CC.C1(C)C=CC(S(O[CH2:55][CH:56]([F:58])[F:57])(=O)=O)=CC=1>CN(C=O)C>[F:57][CH:56]([F:58])[CH2:55][O:1][CH:2]1[C:7]([O:8][CH3:9])([O:10][CH3:11])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1

Participants

5

Reactant 3

HCID 27823122,2-Difluoroethyl (4-methylphenyl)sulphonateHCID 11425480Tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648630tert-Butyl 3-(2,2-difluoroethoxy)-4,4-dimethoxypiperidine-1-carboxylateYield 84.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The same operation as in Example (90a) was performed using tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate (4.6 g, 17.6 mmol), sodium hydride (55% content, 1g, 22.9 mmol), 2,2-difluoroethyl p-toluenesulfonate (5 g, 21.6 mmol) and DMF (50 mL). The residue was purified by column chromatography (elution solvent: hexane/ethyl acetate=10/1, 4/1, 2/1) to obtain 4.85 g of the title compound as a colorless oily substance (85%).

Workup

  1. customThe residue was purified by column chromatography (elution solvent: hexane/ethyl acetate=10/1, 4/1, 2/1)

Sources & evidence

ORD record
ord-b17edcc2b25b42268593dd2220704259
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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