Dimethylformamide → Tert-butyl 3-(3-fluoropropoxy)-4,4-dimethoxypiperidine-1-carboxylate

HRID 43705Notes

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.[H-].[Na+].C1(C)C=CC(S(OC[CH:32]([F:34])[CH3:33])(=O)=O)=CC=1.[CH3:36]N(C=O)C>>[F:34][CH2:32][CH2:33][CH2:36][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

Reactant 4

HCID 6228Dimethylformamide

HCID 24758Sodium hydride

HCID 11425480Tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate

HCID 127568612-Fluoropropyl 4-methylbenzenesulfonate

Product 1

HCID 68406106Tert-butyl 3-(3-fluoropropoxy)-4,4-dimethoxypiperidine-1-carboxylate

Procedure

The same operation as in Example (90a) was performed using tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate (6.4 g, 24.5 mmol), sodium hydride (55% content, 1.33 g, 30.6 mmol), 2-fluoropropyl p-toluenesulfonate (described in Costa, Brian de; Radesca, Lilian; Dominguez, Celia; Paolo, Lisa Di; Bowen, Wayne D.; J. Med. Chem.; 35; 12; 1992; 2221-2230, 7.1 g, 30.6 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 1.39 g of the title compound as a colorless oily substance (18%).

Workup

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

Sources & evidence

ORD record: ord-1be9a5992fa842deb58436d79baaf2e9
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08536197B2

Reaction notes

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