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

HRID 387189
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HRID 387189 반응식
[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>[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]([O:41][CH3:47])=[O:40]
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참가 물질

5

반응물 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]-

생성물 1

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

시약·촉매·용매 1

HCID 702
Ethanol
용매

실험 절차

(±)-{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.

후처리

  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

출처 및 근거

ORD 기록
ord-ecd86ec3039549f58753251f42d17db1
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08372972B2

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