Methyl iodide → 6'-(3-Fluoropropoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one
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][CH:18]([OH:21])[CH2:17][CH2:16]3)[C:12]2=[O:15])=[CH:8][CH:7]=1.[CH3:22]C(C)([O-])C.[K+].CI.CCOC(C)=O>O1CCCC1.CCCCCCC>[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]([O:21][CH3:22])[CH2:19][CH2:20]3)[C:12]2=[O:15])=[CH:8][CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
6′-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 64, 1.94 g, 6.64 mmol) was dissolved in tetrahydrofuran (35 mL) under argon and cooled to 0° C. Potassium tert-butoxide (2.23 g, 19.9 mmol) was added portion wise and the mixture was stirred at 0° C. for 15 min. Methyl iodide (0.83 mL, 13.3 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 over MgSO4 and concentrated in vacuo. The product was isolated using flash chromatography using a gradient of EtOAc (0-50%) in heptane to give 0.611 g (30% yield) of the title compound: MS (ES+) m/z 307 [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 over MgSO4
- concentrationconcentrated in vacuo
- customThe product was isolated
Sources & evidence
- ORD record
- ord-51f475639f664bdb954dbb6431d20c87
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09248129B2
Reaction notes
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