Potassium Phosphate, Tribasic → tert-butyl 5-(4-(methoxycarbonyl)phenyl)-2H-1,4-oxazine-4(3H)-carboxylate

HRID 1615423Notes

Reaction equation

HRID 1615423 reaction equation
O(P(O[C:18]1[N:19]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:21][O:22][CH:23]=1)(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH3:31][O:32][C:33]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)=[O:34].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:31][O:32][C:33]([C:35]1[CH:40]=[CH:39][C:38]([C:18]2[N:19]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:20][CH2:21][O:22][CH:23]=2)=[CH:37][CH:36]=1)=[O:34]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343694-Methoxycarbonylphenylboronic acidHCID 86680661tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate

Product 1

HCID 86680662tert-butyl 5-(4-(methoxycarbonyl)phenyl)-2H-1,4-oxazine-4(3H)-carboxylateYield 50.3%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

Tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate (20 g, 46.1 mmol) and (4-methoxycarbonylphenyl)boronic acid (9.0 g, 49.8 mmol) were dissolved in acetonitrile (300 ml). A solution of potassium phosphate (19.6 g, 92.3 mmol) in water (75 ml) was added, followed by bis(tri-tert-butylphosphine)palladium (0) (2.36 g, 4.61 mmol). Nitrogen was bubbled through the stirred mixture for 40 minutes, then the mixture was heated to 65° C. for 2 hours. The mixture was cooled and diluted with ethyl acetate (1 L) and water (200 ml). The organic phase was separated and washed with sat NaHCO3 (3×200 ml), then brine (200 ml), dried (MgSO4), filtered and partially concentrated to 50 ml. Solid material was removed by filtration (700 mg). The filtrate was concentrated to a brown solid. The crude was purified on silica gel, eluting with 0-10% ethyl acetate/petrol. This gave the title compound as a white solid (7.4 g, 50%); 1H-NMR (CDCl3) 1.13 (9H, s), 3.80 (2H, t), 3.93 (3H, s), 4.20 (2H, t), 6.36 (1H, s), 7.31 (2H, d), 7.98 (2H, d); 13C-NMR (CDCl3) 27.7, 41.5, 52.0, 66.8, 124.5, 129.6, 133.7; MS ES(+) 264.1 (M+-tBu); Anal. Calcd for C12H21NO5: C, 63.94; H, 6.63; N, 4.38. Found: C, 63.83; H, 6.53; N, 2.23.

Workup

  1. customNitrogen was bubbled through the stirred mixture for 40 minutes
  2. temperatureThe mixture was cooled
  3. additiondiluted with ethyl acetate (1 L) and water (200 ml)
  4. customThe organic phase was separated
  5. washwashed with sat NaHCO3 (3×200 ml)
  6. dry with materialbrine (200 ml), dried (MgSO4)
  7. filtrationfiltered
  8. concentrationpartially concentrated to 50 ml
  9. customSolid material was removed by filtration (700 mg)
  10. concentrationThe filtrate was concentrated to a brown solid
  11. customThe crude was purified on silica gel
  12. washeluting with 0-10% ethyl acetate/petrol

Sources & evidence

ORD record
ord-bbc1ff5ab7594334859935a5c5c5d912
Source dataset
uspto-grants-2014_07
Patent number
US08765751B2

Reaction notes

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