Methanol → 4-(1-(tert-Butoxycarbonyl)-3-fluoropiperidin-4-yl)benzoic acid

HRID 1427002Notes

Reaction equation

HRID 1427002 reaction equation
[F:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16]C)=[O:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:3]1.CO.O.[OH-].[Li+]>O1CCCC1>[C:21]([O:20][C:18]([N:4]1[CH2:5][CH2:6][CH:7]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[CH:12][CH:13]=2)[CH:2]([F:1])[CH2:3]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 86730315tert-Butyl 3-fluoro-4-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

Product 1

HCID 838559664-(1-(tert-Butoxycarbonyl)-3-fluoropiperidin-4-yl)benzoic acidYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 3-fluoro-4-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate described in Production Example 6-3 (402 mg, 1.19 mmol) was dissolved in tetrahydrofuran (18 mL), methanol (6 mL), and water (4 mL), then a 2 M aqueous lithium hydroxide solution (4.17 mL, 8.34 mmol) was added at room temperature, and then the mixture was stirred for 3 hours. Tetrahydrofuran and methanol were evaporated under vacuum and 1 M hydrochloric acid was added to the residual solution for neutralization. The aqueous layer was extracted with ethyl acetate four times, and the organic layers were combined, dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated and the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-1:4) to obtain the title compound (347 mg, 90%).

Workup

  1. customTetrahydrofuran and methanol were evaporated under vacuum and 1 M hydrochloric acid
  2. additionwas added to the residual solution for neutralization
  3. extractionThe aqueous layer was extracted with ethyl acetate four times
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was evaporated
  7. customthe resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-1:4)

Sources & evidence

ORD record
ord-a53e1b323a8c48e1ac0f433fe19dbae2
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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