Hydrochloric Acid → 6'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

HRID 1468075ノート

反応式

HRID 1468075 の反応式
Cl.[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C:13]2([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]2)[C:12]3=[N:25]S(C(C)(C)C)=O)[CH2:4]1>O1CCOCC1.C([O-])(O)=O.[Na+]>[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15]([CH2:14][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:12]3=[NH:25])=[CH:16][CH:17]=2)[CH2:4]1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 86706722N-(5'-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide2 回

生成物 1

HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine収率 116.4%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

HCl (4 M in 1,4-dioxane, 4.13 mL, 16.5 mmol) was added to a solution of N-(5′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 18, 750 mg, 1.65 mmol) in anhydrous 1,4-dioxane (25 mL). A white precipitate formed immediately and the resulting cloudy mixture was stirred under a nitrogen atmosphere overnight. The mixture was diluted with NaHCO3 (aq.) and extracted with DCM. The organic phase was dried and concentrated, to yield 6′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-imine (672 mg, 1.92 mmol). The imine, trimethyl orthoformate (0.557 mL, 5.08 mmol) and 2-propanol (5 mL) was placed into a MW tube and the mixture was heated at 60° C. in an oil bath. 2-oxopropanethioamide (Intermediate 1, 397 mg, 3.85 mmol) in MeOH (15 mL) was added and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo. The product was isolated using column chromatography (0-50% EtOAc in heptane) to give 106 mg (12% yield) of the title compound. MS (ES+) m/z 435 [M+H]+.

後処理

  1. customA white precipitate formed immediately
  2. extractionextracted with DCM
  3. customThe organic phase was dried
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-55b30e1edd3d48d58326e4253076e6de
出典データセット
uspto-grants-2015_04
特許番号
US09000185B2

反応ノート

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