Benzaldehyde → (4S)-3-{(2R)-2-[(S)-Hydroxy(phenyl)methyl]hex-5-ynoyl}-4-phenyl-1,3-oxazolidin-2-one

HRID 243653Notes

Reaction equation

HRID 243653 reaction equation
[C:1]([N:8]1[C@@H:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:11][O:10][C:9]1=[O:19])(=[O:7])[CH2:2][CH2:3][CH2:4][C:5]#[CH:6].[Cl-].[Mg+2].[Cl-].C(N(CC)CC)C.[CH:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl[Si](C)(C)C>C(OCC)(=O)C>[OH:37][C@H:30]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C@@H:2]([CH2:3][CH2:4][C:5]#[CH:6])[C:1]([N:8]1[C@@H:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:11][O:10][C:9]1=[O:19])=[O:7]

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 5360315Magnesium ChlorideHCID 57907444(4S)-3-hex-5-ynoyl-4-phenyl-1,3-oxazolidin-2-one

Product 1

HCID 57907409(4S)-3-{(2R)-2-[(S)-Hydroxy(phenyl)methyl]hex-5-ynoyl}-4-phenyl-1,3-oxazolidin-2-oneYield 81.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 56.8 g (221 mmol) of (4S)-3-hex-5-ynoyl-4-phenyl-1,3-oxazolidin-2-one from step A above in 265 mL of anhydrous ethyl acetate at ambient temperature under an atmosphere of nitrogen was added 6.31 g (66.2 mmol) of anhydrous magnesium chloride, 61.5 mL (442 mmol) of triethylamine, 26.9 mL (265 mmol) of benzaldehyde and 42.3 mL (331 mmol) of chlorotrimethylsilane and the resulting mixture was stirred for 72 h. The heterogeneous reaction mixture was filtered through a 300 mL plug of silica gel eluting with an additional 1 L of ethyl acetate. The filtrate was evaporated to dryness in vacuo and the residue suspended in 265 mL of methanol and 10 mL of trifluoroacetic acid. The resulting mixture was stirred at ambient temperature under nitrogen for 5 h during which time the reaction became homogeneous. All volatiles were then removed in vacuo and the residue was purified by silica gel chromatography eluting with a 5-15% ethyl acetate in hexanes gradient to afford the title compound as a white solid (65.0 g, 81.2%). 1H NMR (500 MHz, CDCl3): δ 7.30-7.28 (m, 8H), 7.09-7.07 (m, 2H), 5.42 (dd, J=8.7, 3.7 Hz, 1H), 4.76-4.72 (m, 1H), 4.72-4.67 (m, 1H), 4.65 (t, J=8.7 Hz, 1H), 4.18 (dd, J=8.7, 3.7 Hz, 1H), 3.05 (d, J=7.8 Hz, 1H), 2.24 (td, J=7.1, 2.5 Hz, 2H), 2.00-1.93 (m, 2H), 1.67-1.61 (m, 1H). LC-MS: m/z (ES) 346.1 (MH-H2O)+, 386.0 (MNa)+.

Workup

  1. filtrationThe heterogeneous reaction mixture was filtered through a 300 mL plug of silica gel eluting with an additional 1 L of ethyl acetate
  2. customThe filtrate was evaporated to dryness in vacuo
  3. stirringThe resulting mixture was stirred at ambient temperature under nitrogen for 5 h during which time the reaction
  4. customAll volatiles were then removed in vacuo
  5. customthe residue was purified by silica gel chromatography
  6. washeluting with a 5-15% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-44843ead60144189b74e564c519e3f8a
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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