(1-Benzhydrylpiperidin-4-yl)methanol → 4-((1-Benzhydrylpiperidin-4-yl)methoxy)-5-chloro-2-fluorobenzoic acid

HRID 1849884Notes

Reaction equation

HRID 1849884 reaction equation
[CH:1]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][OH:21])[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:22][C:23]1[C:24](F)=[CH:25][C:26]([F:36])=[C:27]([CH:35]=1)[C:28]([O:30]C(C)(C)C)=[O:29].C([O-])(C)(C)C.[K+]>CS(C)=O>[CH:1]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][O:21][C:24]2[C:23]([Cl:22])=[CH:35][C:27]([C:28]([OH:30])=[O:29])=[C:26]([F:36])[CH:25]=2)[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 21993744(1-Benzhydrylpiperidin-4-yl)methanolHCID 23665647Potassium tert-butoxideHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoate

Product 1

HCID 867037644-((1-Benzhydrylpiperidin-4-yl)methoxy)-5-chloro-2-fluorobenzoic acidYield 82%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of (1-benzhydrylpiperidin-4-yl)methanol (370 mg, 1.3 mmol), tert-butyl 5-chloro-2,4-difluorobenzoate (328 mg, 1.3 mmol) and potassium tert-butanolate (295 mg, 2.6 mmol) in DMSO (4 mL) was stirred at room temperature for 16 h. The reaction mixture was quenched by water (50 mL) and extracted with ethyl acetate (10 mL×4). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was washed with ethyl acetate (5 mL) and filtered to afford 4-((1-benzhydrylpiperidin-4-yl)methoxy)-5-chloro-2-fluorobenzoic acid (480 mg, 82%) as a white solid. LCMS (ESI) m/z: 454.2 [M+H]+.

Workup

  1. customThe reaction mixture was quenched by water (50 mL)
  2. extractionextracted with ethyl acetate (10 mL×4)
  3. washThe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washThe residue was washed with ethyl acetate (5 mL)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-d5a06b4d6c504a7caed7a1d1ed47b9c2
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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