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

HRID 417680

Reaktionsgleichung

[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]

Komponenten

Reaktionsbedingungen

Temperatur: 45 °C

Versuchsvorschrift

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%).

Aufarbeitung

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)

Quellen und Nachweise

ORD-Eintrag: ord-d6c2ba39981e48c8a5aae565642acb2f
Quelldatensatz: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08088368B2

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