2,2-Difluoro-2-(fluorosulfonyl)acetic acid → 4-Difluoromethoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 2039232Notes

Reaction equation

[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([CH2:10][OH:11])[CH2:7][N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:4].[F:19][C:20]([F:28])(S(F)(=O)=O)C(O)=O>CC#N.[Cu]I>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([CH2:10][O:11][CH:20]([F:28])[F:19])[CH2:7][N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:4]

Participants

Conditions

Temperature: 45 °C

Procedure

4-Hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (584 mg, 2.25 mmol) and CuI (86 mg, 0.45 mmol) were suspended in MeCN (10 mL). The reaction mixture was heated to 45° C. and difluoro-fluorosulfonyl-acetic acid (0.465 mL, 4.5 mmol) was added dropwise over the course of 30 min. Stirring was continued for another 3 h, after which the reaction mixture was cooled to RT and concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 and brine then dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (19% to 40% EtOAc/Hex) to afford the title compound (394 mg, 57%).

Workup

temperatureafter which the reaction mixture was cooled to RT
concentrationconcentrated
washwashed with saturated aqueous NaHCO3 and brine
dry with materialthen dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude residue was purified by silica column chromatography (19% to 40% EtOAc/Hex)

Sources & evidence

ORD record: ord-616454d1a4fb408982140cf0ec3d4951
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575118B2

Reaction notes

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