Water → Tert-butyl 4-(5-bromo-2-fluorobenzoyl)-4-hydroxypiperidine-1-carboxylate

HRID 2046700Notes

Reaction equation

HRID 2046700 reaction equation
[Br-].[Br-].[Br-].N1C=CC=CC=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20]([C:24]2([C:30]3[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=3[F:37])SCCCS2)([OH:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].N1C=CC=CC=1.[OH2:44]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C(Cl)Cl.O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20]([C:24](=[O:44])[C:30]2[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=2[F:37])([OH:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 113064294-[2-(5-Bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl esterHCID 12591401Pyridine tribromide

Product 1

HCID 11774000Tert-butyl 4-(5-bromo-2-fluorobenzoyl)-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 21908982Water methylene chlorideSolvent

Procedure

Pyridine tribromide (12.7 g, 39.6 mmol) and TBAB (850 mg, 2.64 mmol) were added to a stirred solution of 4-[2-(5-bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (13 g, 26.42 mmol) and pyridine (2.07 ml, 39.63 mmol) in a mixture of DCM/water (5:1, 180 ml). After stirring for 24 h at RT, the solution was poured into water (150 ml) and the product was extracted with DCM. The combined organic layers were washed with water (400 ml), brine (400 ml), dried over Na2SO4, then filtered and evaporated. The crude product was purified by column chromatography (AcOEt/hexane:20/80) to give 9.5 g of 4-(5-bromo-2-fluoro-benzoyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil.

Workup

  1. extractionthe product was extracted with DCM
  2. washThe combined organic layers were washed with water (400 ml), brine (400 ml)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by column chromatography (AcOEt/hexane:20/80)

Sources & evidence

ORD record
ord-56354329337f48e7886261b327275041
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

Loading…