Triethylamine → (RS)-4-(ethoxy-ethoxycarbonyl-methyl)-3,5-difluoro-benzoic acid 2-trimethylsilanyl-ethyl ester

HRID 1247374Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:25])[CH:5]([C:9]1[C:14]([F:15])=[CH:13][C:12](OS(C(F)(F)F)(=O)=O)=[CH:11][C:10]=1[F:24])[O:6][CH2:7][CH3:8])[CH3:2].[CH3:26][Si:27]([CH3:32])([CH3:31])[CH2:28][CH2:29][OH:30].C(N(CC)CC)C.C[CH2:41][O:42]C(C)=O>CS(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:26][Si:27]([CH3:32])([CH3:31])[CH2:28][CH2:29][O:30][C:41](=[O:42])[C:12]1[CH:11]=[C:10]([F:24])[C:9]([CH:5]([O:6][CH2:7][CH3:8])[C:4]([O:3][CH2:1][CH3:2])=[O:25])=[C:14]([F:15])[CH:13]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (RS)-(2,6-difluoro-4-trifluoromethanesulfonyloxy-phenyl)-ethoxy-acetic acid ethyl ester (200 mg) and 2-(trimethylsilyl)ethanol (603 mg) in DMSO (2.5 ml) was added triethylamine (1.8 ml) followed by Pd(OAc)2 (6 mg) and 1,3-bis(diphenylphosphino)propane (11 mg). The flask was put under carbon monoxide and the reaction mixture was stirred 2 h at 70° C. AcOEt (30 ml) was added and it was washed with 1 N HCl (2×40 ml), water (2×40 ml) and brine (30 ml). After drying (MgSO4) the solvent was evaporated. CC (Hept/AcOEt 98:2) afforded 151 mg (76%) of (RS)-4-(ethoxy-ethoxycarbonyl-methyl)-3,5-difluoro-benzoic acid 2-trimethylsilanyl-ethyl ester. Colorless oil. MS 406.6 ([M+NH4]+).

Workup

washit was washed with 1 N HCl (2×40 ml), water (2×40 ml) and brine (30 ml)
dry with materialAfter drying (MgSO4) the solvent
customwas evaporated

Sources & evidence

ORD record: ord-77fd534d589d4fd0b93aaf4e74fb6076
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129238B2

Reaction notes

Loading…