Tert-butyl 4-(5-bromo-2-fluorobenzoyl)-4-hydroxypiperidine-1-carboxylate → tert-Butyl 5-bromo-3-oxo-3H-spiro[benzofuran-2,4'-piperidine]-1'-carboxylate

HRID 518156Notes

Reaction equation

C(O[K])(C)(C)C.[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]([C:21](=[O:30])[C:22]2[CH:27]=[C:26]([Br:28])[CH:25]=[CH:24][C:23]=2F)([OH:20])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]2([C:21](=[O:30])[C:22]3[CH:27]=[C:26]([Br:28])[CH:25]=[CH:24][C:23]=3[O:20]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: 70 °C

Procedure

A 1 M solution of tBuOK (54.10 ml, 54.10 mmol) in THF was added to a solution of 4-(5-bromo-2-fluoro-benzoyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (14.5 g, 36.07 mmol) in THF (200 ml) and the mixture was stirred at 70° C. After 30 min, the solution was poured into ice water (150 ml) and the product was extracted with AcOEt. The combined organic layers were washed with water (50 ml), brine (50 ml), dried over Na2SO4, then filtered and evaporated to give a pale yellow oil. Purification by column chromatography (hexane/AcOEt: 80/20 to AcOEt) gave 1.5 g of 5-bromo-3-oxo-spiro[benzofuran-2(3H), 4′-piperidin]-1′-carboxylic acid tert-butyl ester as a yellow crystalline solid.

Workup

extractionthe product was extracted with AcOEt
washThe combined organic layers were washed with water (50 ml), brine (50 ml)
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customto give a pale yellow oil
customPurification by column chromatography (hexane/AcOEt: 80/20 to AcOEt)

Sources & evidence

ORD record: ord-cd9b898d6c244f35b2c03aac337b5b08
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115148B2

Reaction notes

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