Propanoic acid, 2-bromo-2-methyl-, ethyl ester → 2-Methyl-2-(tetrahydro-pyran-4-ylsulfanyl)-propionic acid ethyl ester

HRID 538627Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH:4]([S:7]C(=O)C)[CH2:3][CH2:2]1.[OH-].[K+].Br[C:14]([CH3:21])([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16]>CCO>[CH2:18]([O:17][C:15](=[O:16])[C:14]([CH3:21])([S:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)[CH3:20])[CH3:19]

Participants

Conditions

Temperature: 40 °C

Procedure

A solution of 153 g (0.96 mol) of thioacetic acid S-(tetrahydro-pyran-4-yl) ester in EtOH (3.5 L) is degassed with nitrogen over 0.5 h and 125 g (2.23 mol) of KOH are added. Then a solution of 250 mL (1.68 mol) of ethyl α-bromoisobutyrate in EtOH (1 L) are added over 0.5 h, during which the temperature increased to 40° C. The reaction is stirred for 18 h at RT under a nitrogen atmosphere. The reaction mixture is filtered, the solid is washed with EtOH (0.5 L) and the filtrate is concentrated under reduced pressure. The crude material is dryloaded onto silica and purified by dry-flash column chromatography (silica, eluent: nheptanes, 2-10% EE) to afford 158 g of 2-methyl-2-(tetrahydro-pyran-4-ylsulfanyl)-propionic acid ethyl ester. Yield: 71%; ESI-MS: 233 [M+H]+

Workup

filtrationThe reaction mixture is filtered
washthe solid is washed with EtOH (0.5 L)
concentrationthe filtrate is concentrated under reduced pressure
custompurified by dry-flash column chromatography (silica, eluent: nheptanes, 2-10% EE)

Sources & evidence

ORD record: ord-03ba5336fd2d48d5ae590f54cfa3d1f4
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865744B1

Reaction notes

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