Triethylamine → 1,1-Dimethylethyl (2S,4R)-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-[[(methylsulfonyl)oxy]methyl]-1-pyrrolidinecarboxylate

HRID 406494

Reaction equation

HRID 406494 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([CH2:21][OH:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[C:17]([O:16][C:14]([N:12]1[CH2:13][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][C@H:11]1[CH2:21][O:22][S:31]([CH3:30])(=[O:33])=[O:32])=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 11078078tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 141170081,1-Dimethylethyl (2S,4R)-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-[[(methylsulfonyl)oxy]methyl]-1-pyrrolidinecarboxylateYield 91.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,4R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (4.72 g, 14.2 mmol) and triethylamine (3.97 mL, 28.5 mmol) in DCM (30 mL) cooled to 0° C. was added methanesulfonyl chloride (1.66 mL, 21.9 mmol). The reaction mixture was stirred overnight while the ice bath was allowed to warm to room temperature. The solvent was removed under reduced pressure and the residue partitioned between EtOAc and water. The organic phase was washed with 1N phosphoric acid (100 mL), water (100 mL), saturated sodium bicarbonate solution (100 mL) and brine (100 mL) and then was dried over magnesium sulfate and concentrated to yield (2S,4R)-tert-butyl-4-(tert-butyldimethylsilyloxy)-2-((methylsulfonyloxy)methyl)pyrrolidine-1-carboxylate (5.34 g, 13.0 mmol) as a colorless oil. RP-HPLC (Table 1, Method f) Rt 6.25 min; m/z: (M−H)− 468.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between EtOAc and water
  3. washThe organic phase was washed with 1N phosphoric acid (100 mL), water (100 mL), saturated sodium bicarbonate solution (100 mL) and brine (100 mL)
  4. dry with materialwas dried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-887e9fb82e894f80845ed863eb55015c
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Linked notes

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