Methyl Acrylate → 6'-(3,3,3-Trifluoropropoxy)spiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione

HRID 1467920Notes

Reaction equation

[F:1][C:2]([F:17])([F:16])[CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][CH2:11][C:12]2=[O:15])=[CH:8][CH:7]=1.[C:18]([O:22]C)(=O)[CH:19]=[CH2:20].[CH3:24][C:25](C)([O-])C.[K+].[OH-].[K+]>[Cl-].[Na+].O.O>[F:1][C:2]([F:16])([F:17])[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:22])[CH2:25][CH2:24]3)[C:12]2=[O:15])=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 6-(3,3,3-trifluoropropoxy)-2,3-dihydro-1H-inden-1-one (Intermediate 16, 0.774 g, 3.17 mmol) and methyl acrylate (0.629 mL, 6.97 mmol) in 2-Me THF (4 mL) was cooled to 0° C. and potassium tert-butoxide (0.427 g, 3.80 mmol) was added in portions. After stirring for 1.5 h at r.t., water (6.0 mL) and potassium hydroxide (0.178 g, 3.17 mmol) were added and the mixture was heated at reflux overnight. The mixture was cooled to r.t. and water and brine was added. The layers were separated and the aqueous layer extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated yielding the title compound (689 mg, 67% yield). 1H NMR (500 MHz, CDCl3) δ ppm 1.82-1.92 (m, 2 H), 2.17-2.27 (m, 2 H), 2.42-2.53 (m, 2 H), 2.60-2.75 (m, 4 H), 3.14-3.20 (m, 2 H), 4.22-4.27 (m, 2 H), 7.19-7.22 (m, 1 H), 7.25 (dd, 1 H), 7.41 (d, 1 H): MS (ES+) m/z 327 [M+H]+.

Workup

temperaturethe mixture was heated
temperatureat reflux overnight
temperatureThe mixture was cooled to r.t.
customThe layers were separated
extractionthe aqueous layer extracted with EtOAc
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated

Sources & evidence

ORD record: ord-ee807594614746d99a0b403245359c4b
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09000182B2

Reaction notes

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