Diisopropylamine → HCID 58552827, compound

HRID 520466Notes

Reaction equation

HRID 520466 reaction equation
[Li][CH2:2]CCC.C(NC(C)C)(C)C.[CH3:13][CH2:14][O:15][C:16]([CH3:18])=[O:17].O=[C:20]1[O:25][C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)=[N:23][C:22]2[C:36]([C:40]([O-:42])=[O:41])=[CH:37][CH:38]=[CH:39][C:21]1=2.C[O-].[Na+]>C1COCC1.CO>[O:25]=[C:20]1[C:21]2[C:22](=[C:36]([C:40]([O:42][CH3:2])=[O:41])[CH:37]=[CH:38][CH:39]=2)[NH:23][C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:34])([F:33])[F:35])[CH:27]=2)=[C:18]1[C:16]([O:15][CH2:14][CH3:13])=[O:17]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 86660236HCID 86660236, compoundHCID 178418339Butyllithium

Product 1

HCID 58552827HCID 58552827, compoundYield 39.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

n-BuLi (4.4 mL, 2.5 M in hexanes, 11.0 mmol) was added to a solution of diisopropylamine (1.57 mL, 11.2 mmol) in THF (30 mL) at −78° C. After stirring for 20 min, EtOAc (1.09 mL, 11.2 mmol) was added. The solution was stirred at −78° C. for 10 min, warmed to 0° C., stirred for 10 min, then cooled back to −78° C. A solution of 4-oxo-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazine-8-carboxylate 42 (2.00 g, 5.72 mmol) in THF (50 mL) was added over 5 min to the reaction mixture and stirring at −78° C. continued for 1 h. The reaction mixture was then allowed to warm to room temperature over 2 h. MeOH (50 mL) was added followed by solid NaOMe (1.62 g, 30 mmol), and the reaction stirred vigorously for 12 h at room temperature. The solution was concentrated to 20 mL total volume in vacuo, H2O (100 mL) was added, and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude residue was purified by MPLC eluting with pentane/EtOAc (10-50%) to give 43 (950 mg, 39% yield).

Workup

  1. stirringThe solution was stirred at −78° C. for 10 min
  2. stirringstirred for 10 min
  3. temperaturecooled back to −78° C
  4. stirringstirring at −78° C.
  5. waitcontinued for 1 h
  6. temperatureto warm to room temperature over 2 h
  7. stirringthe reaction stirred vigorously for 12 h at room temperature
  8. concentrationThe solution was concentrated to 20 mL total volume in vacuo, H2O (100 mL)
  9. additionwas added
  10. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  11. dry with materialThe combined organic layers were dried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe crude residue was purified by MPLC
  14. washeluting with pentane/EtOAc (10-50%)

Sources & evidence

ORD record
ord-1dd5973674314f0ea3378b04d43a7909
Source dataset
uspto-grants-2016_05
Patent number
US09326986B2

Reaction notes

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