4-Toluenesulfonyl chloride → (R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

HRID 1296180Notes

Reaction equation

HRID 1296180 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:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1.CCCCCC>N1C=CC=CC=1.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:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 8058HexaneHCID 688279N-(tert-Butoxycarbonyl)-D-prolinol2×

Product 1

HCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a well-stirred solution of 2-(R)-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (2), 15 g, 75 mmol) in 42 mL of pyridine and 100 mL of dichloromethane at 0° C. was added a solution of 4toluenesulfonyl chloride (15.68 g, 82.55 mmol) in 75 mL of dichloromethane in a dropwise manner while maintaining the reaction temperature below 0° C. After the addition was complete, the temperature of the reaction was allowed to rise to ambient temperature (˜23° C.) and the reaction was stirred for 5 hours, at which time another 5 grams of 4-toluenesulfonyl chloride was added. The reaction was stirred for 15 hours. The reaction mixture was poured into 150 mL of a 2:1 mixture of dichloromethane and hexane. The mixture was washed twice with a mixture of 100 mL of saturated NaH2PO4 (pH=4.1) solution and water, and then washed with 500 mL of a mixture of 100 mL of Na2HPO4 and water. The organic phase was dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography, eluting with 15% EtOAc in hexane to give a clear oil (22.9 g, 86% yield).

Workup

  1. temperaturewhile maintaining the reaction temperature below 0° C
  2. additionAfter the addition
  3. customto rise to ambient temperature
  4. custom(˜23° C.)
  5. additionwas added
  6. washThe mixture was washed twice with a mixture of 100 mL of saturated NaH2PO4 (pH=4.1) solution and water
  7. washwashed with 500 mL of a mixture of 100 mL of Na2HPO4 and water
  8. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. custompurified by flash chromatography
  11. washeluting with 15% EtOAc in hexane

Sources & evidence

ORD record
ord-f7aa9c9f615c47c78e1983c94d24e2db
Source dataset
uspto-grants-2007_07
Patent number
US07244852B2

Reaction notes

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