(5R)-3-Isopropyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one → (3S,5R)-3-Isopropyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,4-oxazin-2-one

HRID 1948814Notes

Reaction equation

HRID 1948814 reaction equation
[CH:1]([C:4]1[C:5](=[O:16])[O:6][CH2:7][C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:9]=1)([CH3:3])[CH3:2]>ClCCl.O=[Pt]=O>[CH:1]([C@@H:4]1[NH:9][C@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:7][O:6][C:5]1=[O:16])([CH3:3])[CH3:2]

Participants

4

Reactant 1

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

Product 1

HCID 12413874(3S,5R)-3-Isopropyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,4-oxazin-2-one

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (5R)-3-isopropyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one (38) (1.03 g, 4.74 mmol, 1.0 equiv.) in anhydrous dichloromethane (50 mL) under an atmosphere of nitrogen was added PtO2 (103 mg, 0.1 equiv.). The mixture was consecutively degassed and purged three times with hydrogen and then stirred for 5 hours under an atmosphere of hydrogen. Filtration through a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo yielded the crude product which was purified by flash column chromatography on silica eluting with petrol and diethyl ether (4:1) to furnish the title product as a waxy solid (662 mg, 64%); m.p. 61.5-62.5° C.; v(max)(KBr) 3326 (N—H—), 2960 (C—H), 1733 (C═O), cm−1; δH (250 MHz, CDCl3) 7.47-7.35 (5H, m, Ph); 4.33-4.18 (3H, m, PhCHCH2), 3.81 (1H, m, NHCH), 2.49, (1H, m, CH(CH3)2), 1.68 (1H, br, NH), 1.09 (3H, dd, J 6.75 Hz, CH(CH3)2×3), 1.05 (3H, dd, J 6.75, CH(CH3)2×3); δc, (62.5 MHz, CDCl3) 170.3, 138.5, 129.3, 129.1, 127.6, 74.9, 64.2, 57.3, 32.0, 19.4, 17.4; m/z (Cl, NH3), 237 (MNH4+, 5%), 220 (100%, MH+), 219 (22%), and 216 (6%); HRMS for C13H18NO2 requires 220.1333 found 220.1338. [α]D20 −92.1 (c 1.45 CHCl3).

Workup

  1. customThe mixture was consecutively degassed
  2. custompurged three times with hydrogen
  3. filtrationFiltration
  4. customthrough a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo
  5. customyielded the crude product which
  6. customwas purified by flash column chromatography on silica eluting with petrol and diethyl ether (4:1)

Sources & evidence

ORD record
ord-b0dd5e32f3be4d8cbb318f1422aeacdc
Source dataset
uspto-grants-2013_03
Patent number
US08399612B2

Reaction notes

Loading…