Ethyl bromoacetate → Ethyl 2-(3,3-bis(4-fluorophenyl)-2-oxopiperidin-1-yl)acetate

HRID 2408844Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:13][CH2:12][CH2:11][NH:10][C:9]2=[O:14])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>O1CCCC1>[F:21][C:18]1[CH:17]=[CH:16][C:15]([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:13][CH2:12][CH2:11][N:10]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:9]2=[O:14])=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To the product from Example 23B (0.43 g, 1.50 mmol) as a solution in tetrahydrofuran (20 mL) was added potassium tert-butoxide (1.0 M in tetrahydrofuran) (1.80 mL, 1.80 mmol) via syringe under nitrogen followed by the addition of ethyl 2-bromoacetate (0.18 mL, 1.65 mmol). The reaction mixture heated at 80° C. and stirred overnight. The reaction mixture was cooled to room temperature, concentrated, diluted with ethyl acetate, washed with water and brine, dried with MgSO4, filtered and concentrated. Silica gel chromatography eluting with ethyl acetate/hexane (1:4) gave the title compound. MS (DCI) m/z 374 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated
additiondiluted with ethyl acetate
washwashed with water and brine
dry with materialdried with MgSO4
filtrationfiltered
concentrationconcentrated
washSilica gel chromatography eluting with ethyl acetate/hexane (1:4)

Sources & evidence

ORD record: ord-810a1770ebc24a62a746dbb976680e10
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815869B2

Reaction notes

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