(Diethylamino)sulfur trifluoride → (2R,3R)-3-Fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

HRID 1527329Notes

Reaction equation

HRID 1527329 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10](O)[C@H:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(S(F)(F)[F:30])CC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([F:30])[C@H:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 109252822-benzyl 1-tert-butyl (2S,3R)-3-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 68284516(2R,3R)-3-Fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

The title compound was prepared in a similar manner as described by L. Demange et al., Tetrahedron Letters 2001, 42, 651-653: To a solution of (2S,3R)-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (360 mg, 1.12 mmol) in CH2Cl2 (30 mL), cooled to −78° C., was added dropwise DAST (0.740 mL, 5.60 mmol). The reaction mixture was stirred at −78° C. for 5 h, and then was allowed to warm to RT and stirred overnight. After cooling to 0° C., the reaction was quenched with MeOH, followed by addition of aqueous NaHCO3 solution. Volatiles were removed under reduced pressure and the residue was taken up in EtOAc. The organics were washed with aqueous NaHCO3 (3×), water and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9) to give the title compound (99% purity by HPLC/215 nm). TLC Rf (EtOAc/c-hexane 1:4)=0.2; MS (LC/MS): 346 [M+Na]+, 268 [MH−tBu]+, 224 [MH−Boc]+; tR (HPLC conditions b): 5.01 min.

Workup

  1. customThe title compound was prepared in a similar manner
  2. temperatureto warm to RT
  3. stirringstirred overnight
  4. temperatureAfter cooling to 0° C.
  5. customthe reaction was quenched with MeOH
  6. additionfollowed by addition of aqueous NaHCO3 solution
  7. customVolatiles were removed under reduced pressure
  8. washThe organics were washed with aqueous NaHCO3 (3×), water and brine
  9. customdried (Phase separator)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:9)

Sources & evidence

ORD record
ord-853c37f9c614425cb06bcaaa070d30f7
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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