(Diethylamino)sulfur trifluoride → 1,2-Pyrrolidinedicarboxylic acid, 4-fluoro-, 1-(1,1-dimethylethyl) 2-methyl ester, (2R,4R)-rel-

HRID 1015520Notes

Reaction equation

HRID 1015520 reaction equation
O[C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.C(N(S(F)(F)[F:24])CC)C.C([O-])(O)=O.[Na+]>ClCCCl>[F:24][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 109777731,2-Pyrrolidinedicarboxylic acid, 4-fluoro-, 1-(1,1-dimethylethyl) 2-methyl ester, (2R,4R)-rel-Yield 100%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of compound obtained in step II (24.5 g, 0.1 mol) in 1,2-dichloroethane (300 mL) cooled to −10° C. was added diethylaminosulfur trifluoride (19.7 mL, 0.15 mol) over a period of 30 minutes. The reaction mixture was stirred at this temperature for 1 h then at room temperature for 16 h. The reaction mixture was quenched by adding mixture of crushed ice (300 g) and solid NaHCO3 (25.2 g, 0.3 mol). The two layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to obtain 1-tert-butyl 2-methyl (2S,4S)-4-fluoropyrrolidine-1,2-dicarboxylate as a viscous liquid (24.7 g) in 100% yield. [α]D −53.3, (c, 1.0, CHCl3). m/z (M+1) 248; 1H NMR (CDCl3) 300 MHz δ 5.20 (ddd, J=3.8, 3.8, 49.1 Hz, 1H), 4.55 (d, J=9.5 Hz, ½H), 4.42 (d, J=8.9 Hz, ½H), 3.90-3.55 (m, 2H), 3.75 (s, 3H), 2.55-2.20 (m, 2H), 1.46 (s, 3H), 1.41 (s, 6H).

Workup

  1. waitat room temperature for 16 h
  2. customThe reaction mixture was quenched
  3. additionby adding
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-7e63bac8c780440699f0c72047efd063
Source dataset
uspto-grants-2011_07
Patent number
US07985759B2

Reaction notes

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