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Acetic Acid → 2-(3-((5-Cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylic acid

HRID 1748203
ノート
印刷プレビュー

反応式

HRID 1748203 の反応式
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37]([C:39]([O:41]C)=[O:40])[CH:36]=[C:35]([F:43])[C:33]=5[N:34]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1.C1COCC1.[OH-].[K+].CC(O)=O>C(OCC)(=O)C.CO>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:17])[F:18])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37]([C:39]([OH:41])=[O:40])[CH:36]=[C:35]([F:43])[C:33]=5[N:34]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 59053727HCID 59053727、化合物

生成物 1

HCID 590537282-(3-((5-Cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylic acid

試薬・触媒・溶媒 2

HCID 887
Methanol
溶媒
2 回
HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

To a 25-mL round-bottom flask equipped with a stir bar was added sequentially methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylate (0.55 g, 0.89 mmol), 4.0 mL of THF, 2.0 mL of MeOH, and 3 N aqueous KOH solution (1 mL, 3 mmol). The resulting homogenous solution was stirred for 1 hour at 70° C., cooled to RT, and then quenched with AcOH (roughly 0.2 mL of glacial acetic, 3 mmoles) until pH=6 was achieved (Whatman class pH strip paper). At this time the reaction was diluted with ethyl acetate (40 mL) and washed with water (3×5 mL). The ethyl acetate fraction was concentrated under vacuum to give to an oily residue. To the resulting oil was then added 6 mL of MeOH. The oil quickly dissolved, then immediately began to crystallize. Upon standing for 2.5 hrs the mother liquor was withdrawn and crystals washed (3×2 mL of ice cold MeOH). The crystals were dried via vacuum (10 mm Hg pressure at 45° C. overnight) and then recrystallized from acetonitrile, filtered, and dried under vacuum to give the desired product 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylic acid.

後処理

  1. customTo a 25-mL round-bottom flask equipped with a stir bar
  2. temperaturecooled to RT
  3. washwashed with water (3×5 mL)
  4. concentrationThe ethyl acetate fraction was concentrated under vacuum
  5. customto give to an oily residue
  6. dissolutionThe oil quickly dissolved
  7. customto crystallize
  8. waitUpon standing for 2.5 hrs
  9. customthe mother liquor was withdrawn
  10. washcrystals washed (3×2 mL of ice cold MeOH)
  11. customThe crystals were dried via vacuum (10 mm Hg pressure at 45° C. overnight)
  12. customrecrystallized from acetonitrile
  13. filtrationfiltered
  14. customdried under vacuum

出典と根拠

ORDレコード
ord-49e72b9113344c66b3780214941abeca
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09150568B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート