Diisopropylethylamine → (4S)-3-((2R)-3-cyclopentyl-2-{[(phenylmethyl)oxy]methyl}propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one

HRID 1366368Notes

Reaction equation

HRID 1366368 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:22])[CH2:15][CH2:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[CH2:32]([O:39][CH2:40]Cl)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH:17]1([CH2:16][C@H:15]([CH2:40][O:39][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:14]([N:9]2[C@@H:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:12][O:11][C:10]2=[O:13])=[O:22])[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 11077479(4S)-benzyl-3-(3-cyclopentylpropanoyl)oxazolidin-2-one

Product 1

HCID 66936081(4S)-3-((2R)-3-cyclopentyl-2-{[(phenylmethyl)oxy]methyl}propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-oneYield 72%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (4S)-benzyl-3-(3-cyclopentylpropanoyl)oxazolidin-2-one (42.4 g, 141 mmol) in dichloromethane (500 mL) at 0° C. under nitrogen was added titanium (IV) chloride (1 M in DCM, 155 mL, 155 mmol) in a slow steady stream. After 5 min, diisopropylethylamine (27 mL, 155 mmol) was added dropwise. After stirring at 0° C. for 1 h, benzyloxymethylchloride (TCI-America) (39 mL, 280 mmol) was added in a slow steady stream to the resulting titanium enolate, and the mixture was maintained at 0° C. for 3.5 h. The reaction mixture was then quenched with water (400 mL). The aqueous layer was extracted with dichloromethane (150 mL×2). The organic extracts were washed with saturated NaHCO3, were dried (MgSO4) and were evaporated. The residue was washed with ether (2×), and then was triturated with hexanes/ether to provide 2 crops of (4S)-3-((2R)-3-cyclopentyl-2-{[(phenylmethyl)oxy]methyl}propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one as a pale yellow solid (42.7 g, 72%). LCMS: (M+H)+: 422.2.

Workup

  1. temperaturethe mixture was maintained at 0° C. for 3.5 h
  2. customThe reaction mixture was then quenched with water (400 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (150 mL×2)
  4. washThe organic extracts were washed with saturated NaHCO3
  5. dry with materialwere dried (MgSO4)
  6. customwere evaporated
  7. washThe residue was washed with ether (2×)
  8. customwas triturated with hexanes/ether

Sources & evidence

ORD record
ord-57d736a586b4412a9d718d80dad7c599
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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