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

HRID 539302Notes

Reaction equation

HRID 539302 reaction equation
[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

Participants

7

Reactant 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)-dione2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-7c407023f8b94f95aca87b36a0d8f325
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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