Triethylamine → tert-butyl (2S)-2-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylate

HRID 1296176Notes

Reaction equation

HRID 1296176 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][OH:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][S:23]([CH3:22])(=[O:25])=[O:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 643448(S)-(-)-N-Boc-prolinol2×

Product 1

HCID 10039261tert-butyl (2S)-2-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylateYield 96.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(S)-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (2) obtained from above, 109 g, 99.5 g for 100% yield, 0.49 mol) in dichloromethane (500 mL) was cooled to 0° C. Triethylamine (139 mL, 101 g, 1 mol) was added to the cold solution dropwise while maintaining the reaction temperature below 0° C. Methanesulfonyl chloride (58 mL, 85.8 g, 0.75 mol) was added dropwise to reaction mixture while maintaining the reaction temperature at below 0° C. (˜1 hour). The reaction mixture was stirred at room temperature overnight (˜11 hours). HPLC showed absence of starting material. The reaction mixture was quenched with 1 M H3PO4 (300 mL) and mixed for 15 minutes. The organic layer was separated and washed with 1 M aqueous H3PO4 (2×300 mL), followed by saturated aqueous NaHCO3 (4×250 mL), dried over MgSO4, filtered, and concentrated to leave an oily residual product (132 g, 95.6% yield). 1H NMR (CDCl3):δ 1.48 (s, 9H, 3×CH3), 1.82–2.08 (m, 4H, 2×CH2), 3.01 (s, 3H, CH3), 3.36 (m, 2H, CH2), 3.944.18 (m, 2H, CH2) and 4.29 (m, 1H CH); [M+H]+ at m/z 280.

Workup

  1. temperaturewhile maintaining the reaction temperature below 0° C
  2. temperaturewhile maintaining the reaction temperature at below 0° C. (˜1 hour)
  3. customThe reaction mixture was quenched with 1 M H3PO4 (300 mL)
  4. additionmixed for 15 minutes
  5. customThe organic layer was separated
  6. washwashed with 1 M aqueous H3PO4 (2×300 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-bd126dce74c0478c87ebdc7bf893b6b5
Source dataset
uspto-grants-2007_07
Patent number
US07244852B2

Reaction notes

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