Ethyl 3-methyl-2-oxobutyrate → (5R)-3-Isopropyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one

HRID 1948813Notes

Reaction equation

HRID 1948813 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.[CH3:11][CH:12]([CH3:20])[C:13](=O)[C:14](OCC)=[O:15]>C(O)C(F)(F)F>[CH:12]([C:13]1[C:14](=[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)([CH3:20])[CH3:11]

Participants

4

Reactant 2

HCID 88406Ethyl 3-methyl-2-oxobutyrateHCID 2724025(R)-beta-aminophenethyl alcohol

Product 1

HCID 59843746(5R)-3-Isopropyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-oneYield 36%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

(R)-2-phenylglycinol (4) (2.00 g, 14.6 mmol, 1.0 equiv.) and ethyl 3-methyl-2-oxobutyrate (2.20 mL, 14.6 mmol. 1.0 equiv.) were refluxed in trifluoroethanol (30 mL) over activated 4 molecular sieves (7.0 g) for 24 hours. Filtration through a short pad of Celite® 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 (4:1) to furnish the title compound as a colourless oil (1.13 g, 36%); v(max)(film) 2965 (C—H), 1740 (C═O), 1638 (C═N) cm−1; δH (250 MHz, CDCl3) 7.45-7.32 (5H, m, Ph), 4.90-4.83 (1H, m, PhCH), 4.55 (1H, dd, J 4.4 Hz, T 11.5 Hz, 6β-H), 4.13 (1H, dd/10.9 Hz, T 11.4 Hz, 6α-H), 3.32 (1H, m, CH(CH3)2), 1.25 (3H, d, J 5.0 Hz, CH(CH3)2×3), 1.22 (3H, d, /5.0 Hz, CH(CH3)2×3); δc (62.5 MHz, CDCl3) 167.7, 155.7, 137.5, 129.3, 128.6, 127.4, 71.7, 59.7, 32.7, 20.7, 19.9: m/z (CL, NH3), 220 (100%), 218 (MH+, 17%), 217 (27%), and 216 (25%); HRMS for C13H16NO2 requires 218.1177 found 218.1181. [α]D20-207.5 (c 1.17 CHCl3).

Workup

  1. customfor 24 hours
  2. filtrationFiltration
  3. customthrough a short pad of Celite® 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 (4:1)

Sources & evidence

ORD record
ord-5748f5a5301d49ba93b62d899eb3addb
Source dataset
uspto-grants-2013_03
Patent number
US08399612B2

Reaction notes

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