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

HRID 877890Notes

Reaction equation

HRID 877890 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-a032c5604b694cbea9b1b2570edb7e8b
Source dataset
uspto-grants-2015_03
Patent number
US08987442B2

Reaction notes

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