4-Toluenesulfonyl chloride → (1R,3S,5R)-3-(Toluene-4-sulfonyloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester

HRID 1527442Notes

Reaction equation

HRID 1527442 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([CH2:14][OH:15])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>N1C=CC=CC=1.CCOCC>[C:1]([O:5][C:6]([N:8]1[C@H:13]([CH2:14][O:15][S:22]([C:19]2[CH:20]=[CH:21][C:16]([CH3:26])=[CH:17][CH:18]=2)(=[O:24])=[O:23])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 57611064(1R,3S,5R)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 1

HCID 86673858(1R,3S,5R)-3-(Toluene-4-sulfonyloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolvent

Procedure

To an ice-cooled solution of (1R,3S,5R)-3-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (0.480 g, 2.15 mmol) in pyridine (5 mL) was added 4-toluenesulfonyl chloride (0.490 g, 2.58 mmol). The reaction mixture was stirred at RT for 6 h and then diluted with Et2O. The organic phase was washed with 1N HCl (3×), aqueous NaHCO3 (3×) and NaCl, then dried (phase separator) and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (eluent gradient: c-hexane to c-hexane/EtOAc 4:1) to afford the title compound as a colorless wax. TLC, Rf (c-hexane/EtOAc 4:1)=0.2. MS (LC-MS): 390.0 [M+Na]+, 757.0 [2M+H]+. tR (HPLC conditions k): 4.07 min.

Workup

  1. washThe organic phase was washed with 1N HCl (3×), aqueous NaHCO3 (3×) and NaCl
  2. customdried (phase separator)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography on silica gel (eluent gradient: c-hexane to c-hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-cba0b17d4c1540e1bd6c697b64e9dc39
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…