2,6-Lutidine → HCID 59015783, compound

HRID 2113610Notes

Reaction equation

HRID 2113610 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[CH:5](CCl)[CH2:6][C:7]1[N:16]=[C:15](O)[C:14]2[C:9](=[CH:10][C:11]([C:18]3[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:12][CH:13]=2)[N:8]=1)[CH3:2].O=P(Cl)(Cl)[Cl:33].N1C(C)=CC=CC=1C>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:30])[CH2:5][CH2:6][C:7]1[N:16]=[C:15]([Cl:33])[C:14]2[C:9](=[CH:10][C:11]([C:18]3[C:23]([C:24]([F:25])([F:27])[F:26])=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:12][CH:13]=2)[N:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 178471585HCID 178471585, compound

Product 1

HCID 59015783HCID 59015783, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Reflux a mixture of 2-chloromethyl-3-[4-hydroxy-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-2-yl]-propionic acid ethyl ester (600 mg, 1.6 mmol), POCl3 (445 μl, 4.77 mmol), and 2,6-lutidine (596 μl, 4.77 mmol) in CHCl3 (20 ml) for 60 hours. Cool the mixture and concentrate under reduced pressure. Partition the residue between EtOAc and saturated NaHCO3 solution. Wash the EtOAc portion with additional NaHCO3 and then dry (Na2SO4) and concentrate under reduced pressure. Filter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent) and concentrate under reduced pressure to give 3-[4-chloro-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-2-yl]-propionic acid ethyl ester.

Workup

  1. temperatureReflux
  2. temperatureCool the mixture
  3. concentrationconcentrate under reduced pressure
  4. customPartition the residue between EtOAc and saturated NaHCO3 solution
  5. washWash the EtOAc portion with additional NaHCO3
  6. dry with materialdry (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. filtrationFilter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent)
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-57ed9aa2f86d485c9c465933795e78bc
Source dataset
uspto-grants-2008_10
Patent number
US07432275B2

Reaction notes

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