3,4-dihydro-2H-pyran → p-Toluenesulfonic acid

HRID 575522Notes

Reaction equation

HRID 575522 reaction equation
[CH2:1]([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7]O)C.[CH2:10]1[CH2:15]O[CH:13]=[CH:12][CH2:11]1.CC1(C)C2([CH2:25][S:26]([OH:29])(=[O:28])=[O:27])C(CC1CC2)=O>N1C=CC=CC=1>[CH2:5]1[CH2:4][O:3][CH:1]=[CH:7][CH2:6]1.[CH3:1][C:11]1[CH:12]=[CH:13][C:25]([S:26]([OH:29])(=[O:28])=[O:27])=[CH:15][CH:10]=1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 357772Ethyl 4-hydroxybutanoate

Product 2

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyran

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Scheme 7 depicts the synthesis of intermediate 11e wherein R3 and Y2 are the same and X═Br. Thus, commercially-available 4-hydroxy-butanoic acid ethyl ester 37 is treated with DHP and CSA, or with DHP, TsOH, and pyridine to provide ester 38. Reduction with LiAlD4 affords deuterated alcohol 39, which is treated with either triphenyl phosphine in CCl4 (Sabitha, G et al., Tetrahedron Letters, 2006, (volume date 2007), 48(2): 313-315) or with methanesulfonyl chloride, lithium chloride, and 2,6-lutidine in DMF (Blaszykowski, C et al., Organic Letters, 2004, 6(21): 3771-3774) to afford chloride 40. Following the same methods as in Scheme 6, chloride 40 may be converted to 11e.

Sources & evidence

ORD record
ord-e11b9b9cd96346c0b89003efbd971abb
Source dataset
uspto-grants-2015_05
Patent number
US09035050B2

Reaction notes

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