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Sodium Bicarbonate → (R)-2-(8-Fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid

HRID 661331
ノート
印刷プレビュー

反応式

HRID 661331 の反応式
CC1C=CC(C(O[C@H]([C@@H](OC(=O)C2C=CC(C)=CC=2)C(O)=O)C(O)=O)=O)=CC=1.C[O:30][C:31](=[O:70])[CH2:32][CH:33]1[C:42]2[C:37](=[C:38]([F:43])[CH:39]=[CH:40][CH:41]=2)[N:36]=[C:35]([N:44]2[CH2:49][CH2:48][N:47]([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([O:56][CH3:57])[CH:51]=3)[CH2:46][CH2:45]2)[N:34]1[C:58]1[CH:63]=[C:62]([C:64]([F:67])([F:66])[F:65])[CH:61]=[CH:60][C:59]=1[O:68][CH3:69].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:43][C:38]1[CH:39]=[CH:40][CH:41]=[C:42]2[C:37]=1[N:36]=[C:35]([N:44]1[CH2:45][CH2:46][N:47]([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([O:56][CH3:57])[CH:51]=3)[CH2:48][CH2:49]1)[N:34]([C:58]1[CH:63]=[C:62]([C:64]([F:67])([F:66])[F:65])[CH:61]=[CH:60][C:59]=1[O:68][CH3:69])[C@@H:33]2[CH2:32][C:31]([OH:70])=[O:30]
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 516892Sodium BicarbonateHCID 86633821(2R,3R)-2,3-Bis[(4-methylbenzoyl)oxy]succinic acid methyl {8-fluoro-2-[4-(3-methoxyphenyl)-piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate

生成物 1

HCID 57857528(R)-2-(8-Fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid収率 91.6%

試薬・触媒・溶媒 1

HCID 8857
Ethyl Acetate
溶媒

実験手順

(2R,3R)-2,3-Bis[(4-methylbenzoyl)oxy]succinic acid-methyl{8-fluoro-2-[4-(3-methoxyphenyl)-piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate (1:1 salt) (170 g) are suspended in ethyl acetate (850 ml) and shaken with saturated aqueous sodium bicarbonate solution (850 ml) until both phases are clear (ca. 5 min.). The phases are separated, and the solvent of the organic phase is replaced at normal pressure with 1,4-dioxane up to a final temperature of 99° C. (a total of 2.55 l of solvent is distilled off and 2.55 l of 1,4-dioxane are employed in portions). The mixture is cooled to room temperature and stirred at room temperature for 18 h with 1N sodium hydroxide solution (525 ml). Subsequently, the pH is adjusted to 7.5 using concentrated hydrochloric acid (ca. 35 ml), MIBK (850 ml) is added, then the pH is readjusted to 7.0 using concentrated hydrochloric acid (ca. 10 ml). The phases are separated, and the organic phase is dried over sodium sulphate and concentrated. The residue is dissolved in ethanol (350 ml) and concentrated, then again dissolved in ethanol (350 ml) and concentrated at 50° C. A total of 91.6 g of (R)-{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid are thus obtained as an amorphous solid, corresponding to 91.6% of theory.

後処理

  1. custom(ca. 5 min.)
  2. customThe phases are separated
  3. customtemperature of 99° C.
  4. distillationis distilled off
  5. additionis added
  6. customThe phases are separated
  7. dry with materialthe organic phase is dried over sodium sulphate
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in ethanol (350 ml)
  10. concentrationconcentrated
  11. dissolutionagain dissolved in ethanol (350 ml)
  12. concentrationconcentrated at 50° C

出典と根拠

ORDレコード
ord-5d34c19ce6f1486da6945e29c949bab8
出典データセット
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08084604B2

反応ノート

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