Ammonium Chloride → tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate

HRID 1615422Notes

Reaction equation

HRID 1615422 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].C[Si](N([Li])[Si](C)(C)C)(C)C.[P:25](Cl)(=[O:40])([O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[O:33]([P:25]([O:1][C:2]1[N:3]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:5][O:6][CH:7]=1)([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:40])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 75654Diphenyl chlorophosphateHCID 15000282Tert-butyl 3-oxomorpholine-4-carboxylateHCID 178418261HCID 178418261, compound

Product 1

HCID 86680661tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

Tert-butyl 3-oxomorpholine-4-carboxylate (5.2 g, 25.8 mmol) was dissolved in dry THF (52 ml). The mixture was cooled to −30° C. and (bis(trimethylsilyl)amino) lithium (1M THF solution, 28.4 ml, 28.4 mmol) was added dropwise. The resulting mixture was stirred for 1 hr, then diphenyl phosphorochloridate (7.3 g, 27.1 mmol) was added dropwise. The resulting mixture was allowed to warm slowly to ambient temperature over 6 hrs, after which time no starting material was present by HPLC. The reaction mixture was poured into saturated ammonium chloride solution (100 ml) and diluted with ethyl acetate (100 ml). The organic phase was separated and washed with sat NaHCO3 (50 ml), then brine (50 ml), dried (MgSO4), filtered and concentrated. The residue was purified on silica gel, eluting with 25-30% ethyl acetate/petrol. This gave the title compound as an oil which solidified on standing (7.59 g, 68%); 1H-NMR (CDCl3) 1.35 (9H, s), 3.54 (2H, dt), 3.87 (2H, m), 6.26 (1H, s), 7.11-7.17 (6H, m), 7.24-7.28 (4H, m); 31P-NMR (CDCl3)-16.07; 13C-NMR (CDCl3) 28.1, 42.0, 65.8, 120.0, 120.03, 120.09, 120.13, 125.19, 125.61, 125.62, 129.6, 129.86, 129.9; MS ES(+) 378.0 (M+-tBu).

Workup

  1. temperatureto warm slowly to ambient temperature over 6 hrs
  2. customThe organic phase was separated
  3. washwashed with sat NaHCO3 (50 ml)
  4. dry with materialbrine (50 ml), dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel
  8. washeluting with 25-30% ethyl acetate/petrol

Sources & evidence

ORD record
ord-f85ad6a0c0f64cffa3bc862a81e66cd9
Source dataset
uspto-grants-2014_07
Patent number
US08765751B2

Reaction notes

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