Methyl iodide → 6'-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one
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][CH:20]([OH:23])[CH2:19][CH2:18]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1.[CH3:25]C(C)([O-])C.[K+].CI.CCOC(C)=O>C1COCC1.CCCCCCC>[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]([O:23][CH3:25])[CH2:19][CH2:18]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
6′-((3,3-difluorocyclobutyl)methoxy)-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′ (3′H)-one (Intermediate 13, 2.98 g, 8.85 mmol) was dissolved in THF (35 mL) under an atmosphere of nitrogen, and the solution was cooled to 0° C. Potassium tert-butoxide (2.98 g, 26.6 mmol) was added portionwise and the mixture was stirred at 0° C. for 15 min. Methyl iodide (1.11 mL, 17.7 mmol) was added. The cooling bath was removed, and the mixture was stirred at r.t. overnight. Water (200 mL) was added and the resulting solution was partitioned between additional water (200 mL) and EtOAc (400 mL). The organic phases was dried (MgSO4) and concentrated, and the product was isolated using column chromatography (0-50% EtOAc in heptane) providing 1.85 g (59% yield) of the title compound. MS (ES+) m/z 351 [M+H]+.
Workup
- customThe cooling bath was removed
- stirringthe mixture was stirred at r.t. overnight
- additionWater (200 mL) was added
- customthe resulting solution was partitioned between additional water (200 mL) and EtOAc (400 mL)
- dry with materialThe organic phases was dried (MgSO4)
- concentrationconcentrated
- customthe product was isolated
Sources & evidence
- ORD record
- ord-2872036075ba41ef9f87f3db67ef2b89
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09000185B2
Reaction notes
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