Potassium Hydroxide → HCID 67973596, compound

HRID 1184710Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[C:21](Cl)=[CH:20][N:19]=[C:18]([C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][C:24]=3[F:33])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-:34].[K+].C(P(C(C)(C)C)C1(C(C)C)CC(C(C)C)=CC(C(C)C)=C1C1C=CC=CC=1)(C)(C)C>O1CCOCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:34][C:21]3=[CH:20][N:19]=[C:18]([C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][C:24]=4[F:33])[CH:17]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-[5-chloro-2-(2-fluoro-4-methanesulfonyl-phenyl)-pyridin-4-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester (208 mg), potassium hydroxide (70 mg), Pd2(dibenzylidenactone)3*CHCl3 complex (10 mg), and 2-di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (14 mg) in a mixture of 1,4-dioxane (4 mL) and water (2 mL) is heated under an argon atmosphere in an oil bath at 110° C. for 1 h. The reaction mixture is mixed with water and extracted with ethyl acetate. The combined extracts are washed with brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1) to give the title compound. LC (method 7): tR=1.41 min; Mass spectrum (ESI+): m/z=475 [M+H]+.

Workup

extractionextracted with ethyl acetate
washThe combined extracts are washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1)

Sources & evidence

ORD record: ord-b5f1c460181749a4ad799a04265f0a3c
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669271B2

Reaction notes

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