Ethyl pyruvate → (5S)-3-methyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one

HRID 1666921Notes

Reaction equation

HRID 1666921 reaction equation
[C:1]1([C@@H:7]([CH2:9][OH:10])[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11](OCC)(=[O:15])[C:12]([CH3:14])=O>C(O)C(F)(F)F>[CH3:14][C:12]1[C:11](=[O:15])[O:10][CH2:9][C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=1

Participants

4

Reactant 2

HCID 12041Ethyl pyruvateHCID 1347972-Amino-2-phenylethan-1-ol

Product 1

HCID 57467834(5S)-3-methyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-oneYield 44.2%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

(S)-2-phenylglycinol (3.00 g, 21.9 mmol, 1.0 equiv.) and ethyl pyruvate (2.67 mL, 24.1 mmol, 1.1 equiv.) were refluxed in trifluoroethanol (50 mL) over activated 4 molecular sieves (8.00 g) for 24 hours. Filtration through a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo generated the crude product which was purified by flash column chromatography on silica, eluting with petrol and diethyl ether (7:3) to furnish the title compound as a white solid (1.83 g, 44%); m.p. 70.0-71.0° C. (lit 71.0-72.0° C.); v(max)(KBr) 3007 (C—H), 1735 (C═O), 1640 (C═N) cm−1; δH, (250 MHz, CDCl3) 7.45-7.32 (5H, m, Ph), 4.88-4.81 (1H, m, PhCH), 4.56 (1H, dd, J 4.49 Hz, T 9.48 Hz, 6β-H), 4.25 (1H, dd/13.01 Hz, JT 14.99 Hz, 6α-H), 2.41 (3H, s, CH3); δc (62.5 MHz CDCl3) 160.7, 155.9, 137.2, 129.4, 128.7, 127.5, 71.9, 60.1, 22.2; m/z (CL, NH3), 189 (M+, 25%), 159 (12%), 130 (24%), 104 (100%), 90 (21%), and 78 (6%); HRMS for C11HnNO2 requires 189.0787 found 189.0782. [α]D20 +253.0 (c 0.98 CHCl3) (the enantiomer lit. [α]D20 −237.1 (c 1.11 CHCl3)).

Workup

  1. customfor 24 hours
  2. filtrationFiltration
  3. customthrough a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo
  4. customwas purified by flash column chromatography on silica
  5. washeluting with petrol and diethyl ether (7:3)

Sources & evidence

ORD record
ord-26e8fc2f0e874cdc8104f7f3f0db6f52
Source dataset
uspto-grants-2011_10
Patent number
US08044173B2

Reaction notes

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