Sodium hydride → HCID 86730139, compound

HRID 1850110Notes

Reaction equation

HRID 1850110 reaction equation
[C:1]1([CH:7]2[C:11]3([CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[O:10][C:9](=[O:17])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:18][C:19]1[N:24]=[C:23](Cl)[CH:22]=[CH:21][N:20]=1.[H-].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[Cl:18][C:19]1[N:24]=[C:23]([N:8]2[CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:11]3([CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[O:10][C:9]2=[O:17])[CH:22]=[CH:21][N:20]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 86730133HCID 86730133, compound

Product 1

HCID 86730139HCID 86730139, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-phenyl-1,8-dioxa-3-azaspiro[4.5]decan-2-one (300 mg, 1.286 mmol) and 2,4-dichloropyrimidine (192 mg, 1.286 mmol) in DMF (7 mL) under argon was added NaH (60% wt., 67.9 mg, 2.83 mmol) in two portions. The mixture was stirred for ˜1 hour. The reaction mixture was carefully poured into ice-coiled 0.25N aqueous HCl solution. DCM and aqueous NaHCO3 solution were added. The separated aqueous layer was extracted with DCM (3×) and ethyl acetate (1×). The organic layers (DCM and ethyl acetate containing layers independently) were washed with brine, dried over Na2SO4 and filtered off. The organic layers were combined and concentrated under reduced pressure providing crude 3-(2-chloropyrimidin-4-yl)-4-phenyl-1,8-dioxa-3-azaspiro[4.5]decan-2-one (330 mg) as a yellowish liquid, which was directly used in the next reaction without further purification. LCMS m/z 346.1 (M+H)+, Rt 0.83 min.

Workup

  1. extractionThe separated aqueous layer was extracted with DCM (3×) and ethyl acetate (1×)
  2. washThe organic layers (DCM and ethyl acetate containing layers independently) were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-20c6990c133f49d293e18ba173d5d632
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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