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Methanol → 6'-((3,3-Difluorocyclobutyl)methoxy)-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

HRID 1468071
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HRID 1468071 반응식
[F:1][C:2]1([F:24])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1.CO.[B-][N+](C)(C)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[F:1][C:2]1([F:24])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1
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참가 물질

7

반응물 4

HCID 887MethanolHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 86706719HCID 86706719, 화합물2회

생성물 1

HCID 867067206'-((3,3-Difluorocyclobutyl)methoxy)-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one수율 84.4%

시약·촉매·용매 2

HCID 962Water용매2회
HCID 8028Tetrahydrofuran용매

실험 절차

6′-((3,3-Difluorocyclobutyl)methoxy)spiro[cyclohexane-1,2′-indene]-1′,4(3′H)-dione (Intermediate 12, 3.51 g, 10.5 mmol) were dissolved in the mixture of THF (50 mL) and methanol (4.25 mL, 105 mmol). Borane-trimethylamine complex (1.69 g, 23.1 mmol) was added and the mixture was stirred overnight. Citric acid monohydrate (30.9 g, 147 mmol) was added in one portion, followed by dropwise addition of water (3.78 mL, 210 mmol). The mixture was stirred for 3 h before being diluted with water and extracted with EtOAc (×2). The combined organic phases were dried and concentrated. The product was purified using column chromatography (0-10% MeOH in DCM), providing 2.98 g (quantitative yield) of the title compound. MS (ES+) m/z 337 [M+H]+.

후처리

  1. stirringThe mixture was stirred for 3 h
  2. extractionextracted with EtOAc (×2)
  3. customThe combined organic phases were dried
  4. concentrationconcentrated
  5. customThe product was purified

출처 및 근거

ORD 기록
ord-df6b954a827946d289decb3f70336e22
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09000185B2

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