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

HRID 1468071
Notes
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Reaction equation

HRID 1468071 reaction equation
[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 887MethanolHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 86706719HCID 86706719, compound2×

Product 1

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

Reagents, catalysts & solvents

2
HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-df6b954a827946d289decb3f70336e22
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09000185B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes