Benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)acrylate → 2-(4-(1-(Tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid

HRID 1842903Notes

Reaction equation

HRID 1842903 reaction equation
[Si:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=[CH2:29])[C:19]([O:21]CC3C=CC=CC=3)=[O:20])=[CH:14][C:13]=2[F:30])[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>CCOC(C)=O.[OH-].[OH-].[Pd+2]>[Si:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:29])[C:19]([OH:21])=[O:20])=[CH:14][C:13]=2[F:30])[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 86672144Benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)acrylate

Product 1

HCID 708164012-(4-(1-(Tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acidYield 64%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of crude benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)acrylate (4.14 g) in EtOAc (30 mL) was added 20% Pd(OH)2 (207 mg, 5% moleq.) and stirred under hydrogen gas balloon at RT for 1 h. The Pd(OH)2 was filtered out, filtrate evaporated and resulting residue was purified by silica gel (neutral, 100-200) column using ethyl acetate/PE (3:17) as eluent to get crude 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid (1.8 g, 64% LC-MS, HPLC purity) as off white solid. The crude product on prep HPLC purification provided (1.23 g, 13% yield over 3 steps). [TLC system: EtOAc/PE (1:5), Rf: 0.6].

Workup

  1. filtrationThe Pd(OH)2 was filtered out
  2. customfiltrate evaporated
  3. customresulting residue
  4. customwas purified by silica gel (neutral, 100-200) column

Sources & evidence

ORD record
ord-eae91a715cf14c09956bfc4b3c546634
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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