Carbon Tetrachloride → HCID 58458901, compound

HRID 390330Notes

Reaction equation

HRID 390330 reaction equation
[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([NH:24][CH:25]([C:34]#[N:35])[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)(Cl)[Cl:37].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(#N)C.CCOCC>[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:20])([CH3:21])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]1[NH:24][C:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[C:34]([Cl:37])[N:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 58458921HCID 58458921, compound

Product 1

HCID 58458901HCID 58458901, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

(procedure adapted from Org. Lett. 2004, 6, 629-631). To a solution of 3-(benzyloxy)-N-(1-cyano-2-(4-fluorophenyl)ethyl)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.48 g, 1.01 mmol, 1.0 equiv) and CCl4 (0.24 mL, 2.52 mmol, 2.5 equiv) in acetonitrile (10 mL) under a nitrogen atmosphere, was added PPh3 (0.39 g, 2.52 mmol, 2.5 equiv). The reaction was heated to 45° C. (oil bath). After stirring 18 h, the reaction was cooled to ambient temperature and concentrated in vacuo. The residue was treated with CH2Cl2 (10 mL) and 0.5 M NaOH (20 mL) and stirred vigorously. After stirring 4 h, the mixture was poured into water and extracted with CH2Cl2 (×3). The combined CH2Cl2 extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by silica gel chromatography (20-80% ethyl acetate/hexane) to provide a viscous yellow oil. This oil was taken up in ether and seeded with a crystal of previously isolated material. After crystallization, the solid was filtered to provide the title compound (0.32 g, 64% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.17 (s, 1H), 7.28-7.41 (m, 5H), 6.91-6.96 (m, 4H), 5.27 (s, 2H), 3.95-4.11 (m, 4H), 3.77 (s, 2H), 1.67 (s, 6H); LCMS (ES+, (M+H)+) m/z 495.14.

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. additionThe residue was treated with CH2Cl2 (10 mL) and 0.5 M NaOH (20 mL)
  4. stirringstirred vigorously
  5. stirringAfter stirring 4 h
  6. additionthe mixture was poured into water
  7. extractionextracted with CH2Cl2 (×3)
  8. dry with materialThe combined CH2Cl2 extracts were dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography (20-80% ethyl acetate/hexane)
  11. customto provide a viscous yellow oil
  12. customAfter crystallization
  13. filtrationthe solid was filtered

Sources & evidence

ORD record
ord-a6ffa69679c74da18609ff4c6527870d
Source dataset
uspto-grants-2013_02
Patent number
US08383639B2

Reaction notes

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