Triethylamine → (S)-1-Boc-3-methanesulfonyloxy-pyrrolidine

HRID 2040952Notes

Reaction equation

HRID 2040952 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[CH3:21][S:22]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)(=[O:24])=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 11032777(S)-1-Boc-3-methanesulfonyloxy-pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred, 0° C. solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (10.4 g, 55.5 mmol) and triethylamine (15.5 mL, 0.1111 mole) in CH2Cl2 (150 mL) was added dropwise methanesulfonyl chloride (5.2 mL, 0.06665 mole). When the addition was complete, the reaction mixture was allowed to warm to room temperature, then stirred overnight. The reaction mixture was concentrated under reduced pressure to give a residue that was partitioned between ethyl acetate and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (100% hexane to 70:30 hexane/ethyl acetate). Fractions containing product were combined and concentrated under reduced pressure to give (S)-tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate. 1H NMR (300 MHz, CD3OD) δ ppm 1.47 (s, 9H), 2.14-2.29 (m, 2H), 3.12 (s, 1H), 3.36-3.67 (m, 4H), 5.24-5.30 (m, 1H); MS (DCI/NH3) m/z 266 (M+H)+, 283 (M+NH4)+.

Workup

  1. additionWhen the addition
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto give a residue that
  4. customwas partitioned between ethyl acetate and saturated aqueous sodium carbonate
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel chromatography (100% hexane to 70:30 hexane/ethyl acetate)
  9. additionFractions containing product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b29f3b0b8e5e4791b059dbcf21c6a56d
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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