Imidazole → (S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-one

HRID 716079Notes

Reaction equation

HRID 716079 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7].N1C=CN=C1.[CH3:13][C:14]([Si:17](Cl)([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Si:17]([O:1][C@H:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7])([C:14]([CH3:16])([CH3:15])[CH3:13])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11029774(3S)-3-hydroxypyrrolidin-2-one

Product 1

HCID 10584804(S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of commercial (S)-3-hydroxypyrrolidin-2-one (5 g, 49.5 mmol) in DCM (198 ml) was treated with DMAP (0.199 g, 1.632 mmol), imidazole (6.73 g, 99 mmol), and TBDMS-Cl (8.94 g, 59.3 mmol). The reaction mixture was stirred at rt for 16 h, and then was washed with a satd. NaHCO3 solution. The organic layer was concentrated and the crude reaction product was purified by silica gel chromatogpraphy eluting with 50% ethyl acetate in petroleum ether. The desired product was isolated as a white solid (8.1 g, 76%). LC/MS (M+H)+=216.2. 1H NMR (400 MHz, chloroform-d) δ 6.40 (br. s., 1H), 4.26 (t, J=7.8 Hz, 1H), 3.42-3.34 (m, 1H), 3.29-3.21 (m, 1H), 2.36 (dtd, J=12.7, 7.3, 3.3 Hz, 1H), 2.07-1.96 (m, 1H), 0.91 (s, 9H), 0.15 (d, J=7.0 Hz, 6H).

Workup

  1. washwas washed with a satd
  2. concentrationThe organic layer was concentrated
  3. customthe crude reaction product
  4. customwas purified by silica gel chromatogpraphy
  5. washeluting with 50% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-532b6614f27d4caca3f242999d77162d
Source dataset
uspto-grants-2015_11
Patent number
US09187506B2

Reaction notes

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