Sodium Hydroxide → Tert-butyl 2-(1-(4-bromophenyl)piperidin-4-yloxy)acetate

HRID 57592Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].Br[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([O:14][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Tetrabutylammonium bromide (1.06 g, 3.3 mmol) is added to a solution of 1-(4-bromophenyl)piperidin-4-ol (2.56 g, 10 mmol) in toluene (30 mL). The reaction mixture was cooled to 0° C. and aq. 35% sodium hydroxide (30 mL) was added followed by a drop-wise addition of tert-butyl bromoacetate (2.92 g, 15 mmol). The mixture was then allowed to reach room temperature and was stirred for 17 hours at this temperature. The layers were separated and the organic layer was washed twice with water (4 mL), dried over sodium sulfate, concentrated under vacuum and co-evaporated with petroleum ether. Purification of the crude material by flash column chromatography on silica gel (0-20% ethyl acetate in petroleum ether) yielded the desired pure material 3.08 g as pale yellow solid. MS (m/z): 372 (M+2)+

Workup

customto reach room temperature
customThe layers were separated
washthe organic layer was washed twice with water (4 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated under vacuum and co-evaporated with petroleum ether
customPurification of the crude material by flash column chromatography on silica gel (0-20% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-e0555bf4748e40bda55444f47f18849a
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434726B2

Reaction notes

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