Ethyl Acetate → 4-(5-Chloro-2,3-dihydrofuro[2,3-c]pyridin-2-yl)piperidine-1-carboxylic acid tert-butyl ester

HRID 533117Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([OH:24])[CH2:15][C:16]2[C:21](Br)=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:24][C:21]3=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-[2-(5-bromo-2-chloro-pyridin-4-yl)-1-hydroxy-ethyl]-piperidine-1-carboxylic acid tert-butyl ester (11.60 g), palladium acetate (500 mg), racemic 2-(di-tert-butylphosphino)-1,1′-binaphthyl (1.00 g), and cesium carbonate (14.00 g) in toluene (150 mL) is heated in an oil bath at 110° C. under argon atmosphere for 5 h. After cooling to room temperature, ethyl acetate and water are added and the organic phase is separated, washed with brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 70:30→50:50) to give the title compound. LC (method 3): tR=1.44 min; Mass spectrum (ESI+): m/z=339 [M+H]+.

Workup

temperatureAfter cooling to room temperature
customthe organic phase is separated
washwashed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 70:30→50:50)

Sources & evidence

ORD record: ord-c6e10d9d0e4a4b20abbb8309ab993a55
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853239B2

Reaction notes

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