4-Toluenesulfonyl chloride → tert-butyl N-[(4RS)-4-(p-toluenesulfonyloxymethyl)-4,5-dihydro-2-thiazolyl]carbamate

HRID 1280667Notes

Reaction equation

HRID 1280667 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][S:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:4]1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C(N(CC)CC)C>ClCCl>[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([O:1][CH2:2][CH:3]2[CH2:7][S:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[N:4]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 22747911tert-butyl N-[(4RS)-4-hydroxymethyl-4,5-dihydro-2-thiazolyl]carbamate

Product 1

HCID 22747841tert-butyl N-[(4RS)-4-(p-toluenesulfonyloxymethyl)-4,5-dihydro-2-thiazolyl]carbamateYield 60.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.8 g of tert-butyl N-[(4RS)-4-hydroxymethyl-4,5-dihydro-2-thiazolyl]carbamate, 0.76 g of p-toluenesulphonyl chloride and 0.56 cm3 of triethylamine in 25 cm3 of dichloromethane is stirred for 16 hours at a temperature in the region of 20° C. The solution obtained is concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The evaporation residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 60-200μ; diameter 2 cm; height 25 cm), eluting with a mixture of cyclohexane/ethyl acetate (70/30 by volume) and collecting 30 cm3 fractions. The fractions containing the expected product are combined and then concentrated under the above conditions. 0.8 g of tert-butyl N-[(4RS)-4-(p-toluenesulphonyloxymethyl)-4,5-dihydro-2-thiazolyl]carbamate is obtained in the form of a white solid [1H NMR spectrum (300 MHz, CD3l2, δ in ppm): 1.48 (s: 9H); 2.46 (s: 3H); 3.10 (dd, J=11.5 and 5.5 Hz: 1H); 3.33 (dd, J=11.5 and 8.5 Hz: 1H); 3.97 (dd, J=9.5 and 8 Hz: 1H); 4.06 (dd, J=9.5 and 4.5 Hz: 1H); 4.43 (mt: 1H); 7.36 (d, J=8 Hz: 2H); 7.80 (d, J=8 Hz: 2H); from 8.50 to 9.40 (very broad unresolved complex: 1H)].

Workup

  1. customThe solution obtained
  2. concentrationis concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  3. customThe evaporation residue obtained
  4. customis purified by chromatography at atmospheric pressure on a column of silica gel (particle size 60-200μ; diameter 2 cm; height 25 cm)
  5. washeluting with a mixture of cyclohexane/ethyl acetate (70/30 by volume)
  6. customcollecting 30 cm3 fractions
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-b58255589e4c44eeb9edeb3e831bd75b
Source dataset
uspto-grants-2002_09
Patent number
US06451821B1

Reaction notes

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