Diisopropylethylamine → (4R)-3-[(2S)-3-Methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl]-4-(phenylmethyl)-2-oxazolidinone

HRID 660376Notes

Reaction equation

HRID 660376 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[CH2:30][O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH2:30][O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH:16]([CH3:17])[CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 11391340(4R)-4-Benzyl-3-(3-methylbutanoyl)-1,3-oxazolidin-2-one

Product 1

HCID 46741251(4R)-3-[(2S)-3-Methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl]-4-(phenylmethyl)-2-oxazolidinoneYield 50%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-4-benzyl-3-(3-methylbutanoyl)oxazolidin-2-one (209 g, 0.80 mol) in absolute CH2Cl2 (3 L) at 0° C. under N2 was added dropwise TiCl4 (92.2 mL, 0.84 mol) over 30 min. After 15 min, DIEA (0.864 mol) was added dropwise over 15 min, and stirring was continued for 1 h at 0° C. ((Chloromethoxy)methyl)benzene (222 mL, 1.60 mol) was added dropwise over 90 min at 0° C. After stirring for 20 h at 0° C., the reaction was quenched by addition of 10% aq NH4Cl (800 mL) and H2O (1 L). The aqueous phase was extracted with CH2Cl2 (2×1 L), and the combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography on silica gel to afford (R)-4-benzyl-3-((S)-2-(benzyloxymethyl)-3-methylbutanoyl)oxazolidin-2-one (152 g, 50%). 1H NMR (400 MHz, CDCl3): 0.99 (m, 6H), 2.05 (m, 1H), 2.67 (m, 1H), 3.23 (m, 1H), 3.73 (m, 1H), 3.87 (m, 1H), 4.14 (m, 3H), 4.52 (m, 2H), 4.72 (m, 1H), 7.26 (m, 10H).

Workup

  1. waitwas continued for 1 h at 0° C.
  2. stirringAfter stirring for 20 h at 0° C.
  3. customthe reaction was quenched by addition of 10% aq NH4Cl (800 mL) and H2O (1 L)
  4. extractionThe aqueous phase was extracted with CH2Cl2 (2×1 L)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-c1ab1f0268e4472397087dbb55d55459
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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