Lithium Hexamethyldisilazide → 2-Benzyl 3-(tert-butyl) (2S,3S)-1-benzyl-5-methylenepiperidine-2,3-dicarboxylate

HRID 1664599Notes

Reaction equation

HRID 1664599 reaction equation
[CH2:1]([N:8]([CH2:28][C:29]([CH2:31]I)=[CH2:30])[C@@H:9]([CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH2:1]([N:8]1[CH2:28][C:29](=[CH2:31])[CH2:30][C@H:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:9]1[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 160695741-Benzyl 4-(tert-Butyl) N-Benzyl-N-[2-(iodomethyl)allyl]-L-aspartate

Product 1

HCID 160695752-Benzyl 3-(tert-butyl) (2S,3S)-1-benzyl-5-methylenepiperidine-2,3-dicarboxylateYield 48.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of 1-benzyl 4-tert-butyl (2S)-2-{benzyl[2-(iodomethyl)prop-2-en-1-yl]amino}succinate from step 1c (9.2 g) in THF (50 mL) was added dropwise LiHMDS (1.0 M in THF, 20.2 mL) at −78° C. during a period of 30 min. The mixture was stirred at −78° C. for 1 h, and then was allowed to warm to −30° C. during 3 h. The reaction mixture was quenched with 10% citric acid (10 mL) and diluted with brine (100 mL). The mixture was extracted with ethyl acetate (4×75 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was purified through Combiflash (hexane and ethyl acetate: gradient 0 to 5% during 12 min) to give the desired 2-benzyl 3-tert-butyl (2S,3S)-1-benzyl-5-methylenepiperidine-2,3-dicarboxylate (3.45 g). MS (ESI): 422.3 (M+H+).

Workup

  1. temperatureto warm to −30° C. during 3 h
  2. customThe reaction mixture was quenched with 10% citric acid (10 mL)
  3. additiondiluted with brine (100 mL)
  4. extractionThe mixture was extracted with ethyl acetate (4×75 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified through Combiflash (hexane and ethyl acetate: gradient 0 to 5% during 12 min)

Sources & evidence

ORD record
ord-dab076aa06424dd6bee11b3087a192a9
Source dataset
uspto-grants-2011_10
Patent number
US08039471B2

Reaction notes

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