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

HRID 539302노트

반응식

HRID 539302 반응식
[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]3)[C:12]2=[O:15])=[CH:8][CH:7]=1.CO.[B-][N+](C)(C)C.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.O>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:16][CH2:17][CH:18]([OH:21])[CH2:19][CH2:20]3)[C:12]2=[O:15])=[CH:8][CH:7]=1

참가 물질

7

반응물 4

HCID 887MethanolHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 679795576'-(3-Fluoropropoxy)spiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione2회

생성물 1

HCID 679796486'-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

6′-(3-Fluoropropoxy)spiro[cyclohexane-1,2′-indene]-1′,4(3′H)-dione (Intermediate 63, 3.14 g, 10.8 mmol) were dissolved in tetrahydrofuran (50 mL) and MeOH (4.38 mL, 108 mmol). Borane-trimethylamine complex (1.74 g, 23.8 mmol) was added and the resulting mixture was stirred overnight. Citric acid monohydrate (31.8 g, 151 mmol) was added all at once and was followed by dropwise addition of water (3.90 mL, 216 mmol). The mixture was stirred for 3 h before being diluted with water and extracted with EtOAc (×2). The combined organic phases was dried over MgSO4 and concentrated in vacuo. The product was purified using silica gel flash chromatography using a gradient of MeOH (0-10%) in DCM to give 1.94 (61% yield) of the title compound which was used in the next step without further purification: MS (ES+) m/z 307 [M+H]+.

후처리

  1. stirringThe mixture was stirred for 3 h
  2. extractionextracted with EtOAc (×2)
  3. dry with materialThe combined organic phases was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe product was purified

출처 및 근거

ORD 기록
ord-7c407023f8b94f95aca87b36a0d8f325
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865911B2

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