Methyl iodide → (3R,5S)-1-t-butoxycarbonyl-5-t-butyldiphenylsiloxymethyl-3-methyl-pyrrolidine-2-one

HRID 2879Notes

Reaction equation

HRID 2879 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10][C:9]1=[O:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]N([Si](C)(C)C)[Si](C)(C)[CH3:36].IC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][C@@H:10]([CH3:36])[C:9]1=[O:32])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11762195(S)-tert-Butyl 2-(((tert-butyldiphenylsilyl)oxy)methyl)-5-oxopyrrolidine-1-carboxylateHCID 178418261HCID 178418261, compound

Product 1

HCID 57437936(3R,5S)-1-t-butoxycarbonyl-5-t-butyldiphenylsiloxymethyl-3-methyl-pyrrolidine-2-oneYield 47.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-1-t-butoxycarbonyl-5-t-butyldiphenylsiloxymethyl-pyrrolidine-2-one (15 g, 33 mmol) in THF (250 mL) at -78° C. a 1M solution of LiN(SiMe3)2 (35 mL, 35 mmol) was slowly added. After stirring for 1 hr, iodomethane (6.2 mL, 100 mmol) was added. The reaction mixture was allowed to stir for another 2 hr at -78° C. and then quenched with acetic acid. The mixture was concentrated into half volume, diluted with water (200 mL) and extracted with ethyl acetate (EtOAc). The combined extracts were washed with water, brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue purified by flash column chromatography on silica gel, eluted with EtOAc:Hexane (1:2.5). The desired (2S,5R) isomer was eluted first from the column and crystallized in hexanes to give 7.3 g (47%) of product as white crystals. mp=84°-85° C. 1H NMR (200 MHz, CDCl3): δ 7.62 (m, 5H), 7.40 (m, 5H), 4.12 (m, 1H), 3.85 (dd, J=10.3, 4.7 Hz, 1H), 3.72 (dd, J=10.3, 2.8 Hz, 1H), 2.82 (m, 1H), 2.31 (dd, J=12.7, 8.9 Hz, 1H), 1.75 (m, 1H), 1.42 (s, 9H), 1.20 (d, J=7.0 Hz, 3H), 1.02 (s, 9H).

Workup

  1. stirringto stir for another 2 hr at -78° C.
  2. customquenched with acetic acid
  3. concentrationThe mixture was concentrated into half volume
  4. additiondiluted with water (200 mL)
  5. extractionextracted with ethyl acetate (EtOAc)
  6. washThe combined extracts were washed with water, brine
  7. dry with materialdried over MgSO4
  8. customThe solvent was evaporated in vacuo
  9. customthe residue purified by flash column chromatography on silica gel
  10. washeluted with EtOAc:Hexane (1:2.5)
  11. washwas eluted first from the column
  12. customcrystallized in hexanes

Sources & evidence

ORD record
ord-10d566a7e6924599b73ffe5a8d4c02d6
Source dataset
uspto-grants-1998_03
Patent number
US05731348

Reaction notes

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