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

HRID 661329Notes

Reaction equation

HRID 661329 reaction equation
C[O:2][C:3](=[O:42])[CH2:4][CH:5]1[C:14]2[C:9](=[C:10]([F:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[CH2:18][CH2:17]2)[N:6]1[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:40][CH3:41].[OH-].[Na+]>O1CCOCC1>[F:15][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[N:8]=[C:7]([N:16]1[CH2:17][CH2:18][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[CH2:20][CH2:21]1)[N:6]([C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:40][CH3:41])[CH:5]2[CH2:4][C:3]([OH:42])=[O:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 119836914-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

Product 1

HCID 99160994-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-Yield 102.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3,4-dihydroquinazolin-4-yl}acetate (64 g) is dissolved in 1,4-dioxane (450 ml) and 1N sodium hydroxide solution (325 ml) and stirred at room temperature for 2 h, then some of the solvent is distilled off at 30° C. in vacuo (400 ml). Subsequently, toluene (300 ml) is added and the phases are separated. The aqueous phase is washed with toluene (twice 150 ml), then the combined organic phases are extracted again with 1N sodium hydroxide solution (50 ml). The pH of the combined aqueous phases is adjusted to 7.5 with 2N hydrochloric acid (ca. 150 ml), then MIBK (150 ml) is added. The phases are separated, the aqueous phases are extracted again with MIBK (150 ml), then the combined MIBK phases are dried over sodium sulphate and concentrated at 45° C. A total of 64 g of (±)-{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid are obtained in quantitative yield as an amorphous solid.

Workup

  1. distillationsome of the solvent is distilled off at 30° C. in vacuo (400 ml)
  2. additionSubsequently, toluene (300 ml) is added
  3. customthe phases are separated
  4. washThe aqueous phase is washed with toluene (twice 150 ml)
  5. extractionthe combined organic phases are extracted again with 1N sodium hydroxide solution (50 ml)
  6. additionMIBK (150 ml) is added
  7. customThe phases are separated
  8. extractionthe aqueous phases are extracted again with MIBK (150 ml)
  9. dry with materialthe combined MIBK phases are dried over sodium sulphate
  10. concentrationconcentrated at 45° C

Sources & evidence

ORD record
ord-10bb627a88dc4292b6efb302b29a1c56
Source dataset
uspto-grants-2011_12
Patent number
US08084604B2

Reaction notes

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