Acetic Acid → 3-[(S)-1-(4-Bromo-2-methyl-phenyl)-ethyl]-(R)-6-(2-methyl-allyl)-6-phenyl-[1,3]oxazinan-2-one

HRID 2036542Notes

Reaction equation

HRID 2036542 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Cl[CH2:12][CH2:13][C:14]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([OH:19])[CH2:15][C:16]([CH3:18])=[CH2:17].[Br:26][C:27]1[CH:32]=[CH:31][C:30]([C@@H:33]([N:35]=[C:36]=[O:37])[CH3:34])=[C:29]([CH3:38])[CH:28]=1.C(O)(=O)C>O1CCCC1.O>[Br:26][C:27]1[CH:32]=[CH:31][C:30]([C@@H:33]([N:35]2[CH2:12][CH2:13][C@:14]([CH2:15][C:16]([CH3:18])=[CH2:17])([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[O:19][C:36]2=[O:37])[CH3:34])=[C:29]([CH3:38])[CH:28]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2733832Lithium HexamethyldisilazideHCID 595323881-Chlor-5-methyl-3-phenylhex-5-en-3-olHCID 86649417(S)-4-bromo-1-(1-isocyanato-ethyl)-2-methyl-benzene

Product 1

HCID 581023693-[(S)-1-(4-Bromo-2-methyl-phenyl)-ethyl]-(R)-6-(2-methyl-allyl)-6-phenyl-[1,3]oxazinan-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hexamethyldisilazide (1 mol/L in tetrahydrofuran, 18.7 mL) was added dropwise (at such a rate that the solution temperature maintains below 25° C.) to a solution of 1-chloro-5-methyl-3-phenyl-hex-5-en-3-ol (3.82 g) and (S)-4-bromo-1-(1-isocyanato-ethyl)-2-methyl-benzene (4.49 g) in tetrahydrofuran (140 mL) chilled in an ice bath. The solution was stirred in the cooling bath for 30 min and at room temperature for another 60 min. Then acetic acid (1.9 mL) in water (40 mL) was slowly added to the reaction mixture. The resulting mixture was concentrated under reduced pressure and the residue was taken up in tert-butyl methyl ether. The resulting solution was washed with water, dried (MgSO4), and concentrated. The residue was submitted to chromatography on silica gel (cyclohexane/ethyl acetate 90:10-40:60) to afford the title compound as a colorless solid. Besides the title compound a diastereomer thereof, 3-[(S)-1-(4-bromo-2-methyl-phenyl)-ethyl]-6-(S)-(2-methyl-allyl)-6-phenyl-[1,3]oxazinan-2-one, was isolated as an oil {1.55 g, Mass spectrum (ESI+): m/z=428/430 (Br) [M+H]+}. Yield: 1.34 g (18% of theory); Mass spectrum (ESI+): m/z=428/430 (Br) [M+H]+; 1H NMR (400 MHz, DMSO-d6) 1.40 (d, J=6.8 Hz, 3H), 1.53 (s, 3H), 1.71 (s, 3H), 1.81-190 (m, 1H), 1.98-2.08 (m, 1H), 2.43-ca. 2.51 (m, 3H), 2.86-2.94 (m, 1H), 4.58 (hardly resolved m, 1H), 4.77 (hardly resolved m, 1H), 5.30 (q, J=6.8 Hz, 1H), 7.15-7.19 (m, 2H), 7.24-7.35 (m, 6H). The assignment of the stereogenic centers of the title compound is based on the comparison of the 1H NMR data with the data of the known analog 3-[(S)-1-(4-bromo-phenyl)-ethyl]-(R)-6-(2-methyl-allyl)-6-phenyl-[1,3]oxazinan-2-one.

Workup

  1. custommaintains below 25° C.
  2. temperaturechilled in an ice bath
  3. concentrationThe resulting mixture was concentrated under reduced pressure
  4. washThe resulting solution was washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a65055589aab49ee819f3ae9ff9169bb
Source dataset
uspto-grants-2013_11
Patent number
US08575157B2

Reaction notes

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