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

HRID 2410227Notes

Reaction equation

HRID 2410227 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]([O:41]C)=[O:40].[OH-].[Na+]>O1CCOCC1>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:12]1[CH2:13][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]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]

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-2b3e2239db244bf598e57f4108284cc7
Source dataset
uspto-grants-2014_08
Patent number
US08816075B2

Reaction notes

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