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

HRID 553595Notes

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]>C(O)C>[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 ethanol (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 is increased to 40° C. The reaction is stirred for 18 h at room temperature under a nitrogen atmosphere. The reaction mixture is filtered, the solid is washed with ethanol (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: n-heptanes, 2-10% ethyl acetate) to afford 158 g of 2-methyl-2-(tetrahydro-pyran-4-ylsulfanyl)-propionic acid ethyl ester as an orange-brown oil. Yield: 71%; ES-MS: m/z 233 [M+H]

Workup

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

Sources & evidence

ORD record: ord-17ff8094abbd4a95ae56354ce95e48cb
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08048899B2

Reaction notes

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