Methanesulfonyl chloride → (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylate

HRID 1426895Notes

Reaction equation

HRID 1426895 reaction equation
[Si:1]([O:8][C@H:9]([CH2:19][CH:20]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH3:30])O)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CS(Cl)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:1]([O:8][CH:9]1[CH2:10][N:11]([C:12]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:18])[C@@H:20]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[O:29][CH3:30])[CH2:19]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67470707(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate

Product 1

HCID 67470718(R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylateYield 57.38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-4-(5-fluoro-2-methoxyphenyl)-4-hydroxybutylcarbamate (4.810 g, 10.84 mmol) in CH2Cl2 (108 mL) at −60° C. was added TEA (4.534 mL, 32.53 mmol) followed by methanesulfonyl chloride (0.9231 mL, 11.93 mmol). The resulting mixture was slowly warmed to −5° C. and poured into a mixture of ice and saturated aqueous NaHCO3 (50 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica column chromatography, eluting with 2-10% MeOH/DCM to afford (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine-1-carboxylate (assumed to be a mixture of cis and trans isomers; 2.648 g, 57.38% yield). LC/MS (ES+APCI) m/z=326.1 (M+H-Boc).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with CH2Cl2 (2×50 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude material that
  7. customwas purified by silica column chromatography
  8. washeluting with 2-10% MeOH/DCM

Sources & evidence

ORD record
ord-8acb7243285b477bb3397201b1b63129
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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