(S)-3,5-di-(tert-butyldimethylsilyloxy)-pentan-2-one → (S,4E)-1,3-Di-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-ene

HRID 1700958Notes

Reaction equation

C([Li])CCC.C([C:8]([CH2:19][CH3:20])([C:13]1[N:14]=[C:15]([CH3:18])[S:16][CH:17]=1)P([O-])(=O)[O-])C.[Si:21]([O:28][C@@H:29]([CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])C(=O)C)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C1COCC1>[Si:21]([O:28][CH2:29][CH2:33][C@H:34]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:37])[CH3:38])/[C:19](/[CH3:20])=[CH:8]/[C:13]1[N:14]=[C:15]([CH3:18])[S:16][CH:17]=1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

Conditions

Temperature: -78 °C

Procedure

(see D. Schinzer et al., Chem. Eur. J. 2, 1477-1482 (1996)) n-Butyl lithium (23,5 ml [58.7 mmol, 1.2 equiv] of a 2.5 M solution in hexanes) is added dropwise to a stirred solution of diethyl-(2-methylthiazol-4-yl)-methanephosphonate 10 (14,64 g, 58.7 mmol, 1.2 equiv) in THF (150 ml) cooled to −78° C. After stirring at −78° C. for 1 h, a solution of (S)-3,5-di-(tertbutyidimethylsilyloxy)-pentan-2-one 14 (16.96 g, 48,9 mmol, 1.0 equiv) in 100 ml of THF is added dropwise at −78° C. The mixture is warmed to r.t. within 12 h. The reaction is quenched with saturated aqueous ammonium chloride solution (100 ml). The organic layer is seperated and the aqueous layer is extracted with diethyl ether (3×100 ml). The combined organic extracts are dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by flash column chromatography (gradient elution with pentane/dichloromethane 4:1→dichloromethane→diethyl ether→diethyl ether/methanol 10:1) affords (S,4E)-1,3di-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-ene 15 (17,07 g, 38.6 mmol, 79%) as a colourless oil and some starting material (10 and 14). Alternatively, the crude product obtained after extraction can be directly used in the next step.

Workup

temperatureThe mixture is warmed to r.t. within 12 h
customThe reaction is quenched with saturated aqueous ammonium chloride solution (100 ml)
customThe organic layer is seperated
extractionthe aqueous layer is extracted with diethyl ether (3×100 ml)
dry with materialThe combined organic extracts are dried over magnesium sulfate
concentrationconcentrated in vacuo
customPurification of the residue
washby flash column chromatography (gradient elution with pentane/dichloromethane 4:1→dichloromethane→diethyl ether→diethyl ether/methanol 10:1)

Sources & evidence

ORD record: ord-c777999baaef42d0b0364b5e00460443
Source dataset: uspto-grants-2002_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06350878B1

Reaction notes

Loading…