Lithium Hexamethyldisilazide → (S,E)-tert-butyl 2-(4-(methoxycarbonyl)styryl)pyrrolidine-1-carboxylate

HRID 923444Notes

Reaction equation

C(OP([CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1)(OCC)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:30]([C@@H:32]1[CH2:36][CH2:35][CH2:34][N:33]1[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=O>C1COCC1>[CH3:17][O:16][C:14]([C:13]1[CH:12]=[CH:11][C:10](/[CH:9]=[CH:30]/[C@@H:32]2[CH2:36][CH2:35][CH2:34][N:33]2[C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])=[CH:19][CH:18]=1)=[O:15]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of the product of Example 149A (4.02 g, 14.05 mmol) dissolved in THF (50 mL) and cooled to −78° C. was added lithium bis(trimethylsilyl)amide (1.0M in THF, 12.05 mL, 12.05 mmol) dropwise and the resultant solution stirred at −78° C. for 1 additional hour. Afterwards a solution of (S)-tert-butyl 2-formylpyrrolidine-1-carboxylate (2.0 g, 10.04 mmol) in THF (20 mL) was added dropwise, the cooling bath was then removed and after the reaction reached room temperature it was maintained at this temperature for an additional 3 hours. The solution had EtOAc added to it and the mixture extracted with water. The organic extract was then dried, filtered, concentrated and purified by chromatography (silica gel, 10-50% EtOAc in hexanes) to afford 2.05 g (62%) of the title compound. MS (ESI) m/z 332 (M+H)+.

Workup

customthe cooling bath was then removed
customreached room temperature
temperaturewas maintained at this temperature for an additional 3 hours
additionadded to it
extractionthe mixture extracted with water
extractionThe organic extract
customwas then dried
filtrationfiltered
concentrationconcentrated
custompurified by chromatography (silica gel, 10-50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-d06a38284e4a411faaebe9b1a21870f8
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278922B2

Reaction notes

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