Methanol → 4-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

HRID 661333Notes

Reaction equation

HRID 661333 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:12]1[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH2:14][CH2:13]1)[N:8]([C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1[O:36][CH3:37])[CH:7]2[CH2:38][C:39]([OH:41])=[O:40].S(=O)(=O)(O)O.[CH3:47]O>C(O)C>[CH3:47][O:40][C:39](=[O:41])[CH2:38][CH:7]1[C:6]2[C:11](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=2)[N:10]=[C:9]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH2:16][CH2:17]2)[N:8]1[C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1[O:36][CH3:37]

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 99160994-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-

Product 1

HCID 119836914-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl esterYield 75.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(±)-{8-Fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid (54 g) is dissolved in methanol (540 g), then concentrated sulphuric acid (7.85 ml) is added. The mixture is stirred under reflux for 26 h, then cooled and concentrated in vacuo to ca. one third of the original volume. Water (150 ml) and dichloromethane (150 ml) are added, then the phases are separated. The organic phase is extracted with saturated sodium hydrogencarbonate solution (two times 140 ml), dried over sodium sulphate and concentrated to give a foamy residue. This is dissolved twice in succession in ethanol (150 ml each) and concentrated, and subsequently dried for 18 h in vacuo using entraining nitrogen. A total of 41.6 g of methyl{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate are thus obtained as an amorphous solid, corresponding to 75.2% of theory.

Workup

  1. temperatureunder reflux for 26 h
  2. temperaturecooled
  3. concentrationconcentrated in vacuo
  4. additionWater (150 ml) and dichloromethane (150 ml) are added
  5. customthe phases are separated
  6. extractionThe organic phase is extracted with saturated sodium hydrogencarbonate solution (two times 140 ml)
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated
  9. customto give a foamy residue
  10. concentrationconcentrated
  11. customsubsequently dried for 18 h in vacuo

Sources & evidence

ORD record
ord-0c77cc0e6ad147ceb46473bcdb7872b4
Source dataset
uspto-grants-2011_12
Patent number
US08084604B2

Reaction notes

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