4-Toluenesulfonyl chloride → tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

HRID 51526

Reaction equation

HRID 51526 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:14](Cl)([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15]>N1C=CC=CC=1.C1CCCCC1.C(OCC)C>[CH3:21][C:20]1[CH:22]=[CH:23][C:17]([S:14]([O:13][CH:10]2[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]2)(=[O:16])=[O:15])=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 44169391-Boc-3-pyrrolidinol

Product 1

HCID 13591085tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylateYield 29%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 21895417Cyclohexane diethyletherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-tert-butoxycarbonylpyrrolidin-3-ol (19.8 g, 0.106 mol) in pyridine (200 ml) at 0° C. under nitrogen was added tosyl chloride (22.3 g, 0.117 mol) portionwise. Stir at 0° C. for 2 hr, warm to room temperature and stir at room temperature overnight. The pyridine was evaporated in vacuo and the residue was partioned between EtOAc and saturated aqueous citric acid (200 ml each). The aqueous layer was extracted with EtOAc (2×200 ml) and the combined organics were dried (sodium sulphate), filtered and evaporated to leave an oil which was purified by flash silica gel column chromatography using 10% EtOAc/cyclohexane as eluent to give in F40-85 an oil. The oil was dissolved in a small volume of cyclohexane/diethylether (5:1, 50 ml), cooled and scratched with a spatula to induce crystallisation. The resulting solid was filtered to give tert-butyl 3-[(4-methylphenyl)sulfonyl]oxy-1-pyrrolidinecarboxylate (10.5 g, 29%) as a white solid. Rf in EtOAc/cyclohexane=0.13. 1H NMR (CDCl3, 250 MHz): 7.79 (2H, d), 7.35 (2H, d), 5.04 (1H, m), 3.43 (4H, m), 2.46 (3H, s), 2.03-2.20 (2H, bm), 1.43 (9H, s).

Workup

  1. temperaturewarm to room temperature
  2. stirringstir at room temperature overnight
  3. customThe pyridine was evaporated in vacuo
  4. extractionThe aqueous layer was extracted with EtOAc (2×200 ml)
  5. dry with materialthe combined organics were dried (sodium sulphate)
  6. filtrationfiltered
  7. customevaporated
  8. customto leave an oil which
  9. customwas purified by flash silica gel column chromatography
  10. customto give in F40-85 an oil
  11. temperaturecooled
  12. customcrystallisation
  13. filtrationThe resulting solid was filtered

Sources & evidence

ORD record
ord-d613b500594d49e093ffd3e238a031d2
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Linked notes

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