Thioglycolic Acid → (2S)-2-[((S)-6-Methoxy-alpha-methyl-2-naphthalenacetyloxy)methyl]-1,3-oxathiolan-5-one

HRID 844517Notes

Reaction equation

HRID 844517 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:23])[C:14]([O:16][CH2:17][CH:18](OC)OC)=[O:15])[CH:7]=[CH:6]2.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.S([O-])([O-])(=O)=O.[Mg+2].[SH:45][CH2:46][C:47]([OH:49])=[O:48]>ClC(Cl)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:23])[C:14]([O:16][CH2:17][C@@H:18]1[S:45][CH2:46][C:47](=[O:49])[O:48]1)=[O:15])[CH:7]=[CH:6]2

Participants

6

Reactant 4

HCID 1133Thioglycolic AcidHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 867580112,2-dimethoxyethyl (S)-6-methoxy-alpha-methyl-2-naphthaleneacetate

Product 1

HCID 70161980(2S)-2-[((S)-6-Methoxy-alpha-methyl-2-naphthalenacetyloxy)methyl]-1,3-oxathiolan-5-oneYield 53.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

To a round bottom flask is added 2,2-dimethoxyethyl (S)-6-methoxy-α-methyl-2-naphthaleneacetate (13.8 g), dichloroethane (60 mL), camphorsulfonic acid (0.7 g) and magnesium sulfate (1.0 g). The reaction mixture is heated to reflux and a solution of mercaptoacetic acid (13.5 g) in dichloroethane (15 mL) is added dropwise. The mixture is removed from the oil bath and a sample is taken for TLC and NMR analysis. Additional camphorsulfonic acid (0.6 g) is added and the mixture is heated in an oil bath to reflux for 2 hours. The mixture is cooled to room temperature and then shaken with water (50 mL) and saturated sodium bicarbonate (50 mL). The separated lower phase is shaken with saturated sodium bicarbonate (25 mL) and water (50 mL), the phases are separated and the lower cloudy organic phase is vacuum concentrated to give 17.4 g of crude product. The obtained syrup is applied to a silica column and eluted with EtOAc/heptanes (15:85) to provide 8.0 g of product.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux
  3. customThe mixture is removed from the oil bath
  4. additionAdditional camphorsulfonic acid (0.6 g) is added
  5. temperaturethe mixture is heated in an oil bath
  6. temperatureto reflux for 2 hours
  7. customThe separated lower phase
  8. stirringis shaken with saturated sodium bicarbonate (25 mL) and water (50 mL)
  9. customthe phases are separated
  10. concentrationconcentrated
  11. customto give 17.4 g of crude product
  12. washeluted with EtOAc/heptanes (15:85)

Sources & evidence

ORD record
ord-397ce8a51bc8457c8d4d5dcc8db588cf
Source dataset
uspto-grants-2002_04
Patent number
US06380388B1

Reaction notes

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