Methyl Acrylate → HCID 86706719, compound

HRID 1468070Notes

Reaction equation

HRID 1468070 reaction equation
[F:1][C:2]1([F:18])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][CH2:13][C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1.[C:19]([O:23]C)(=O)[CH:20]=[CH2:21].[CH3:25][C:26](C)([O-])C.[K+].[OH-].[K+]>[Cl-].[Na+].O.O>[F:1][C:2]1([F:18])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:21][CH2:20][C:19](=[O:23])[CH2:26][CH2:25]4)[C:14]3=[O:17])=[CH:10][CH:9]=2)[CH2:3]1

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 14797Potassium HydroxideHCID 23665647Potassium tert-butoxideHCID 867067186-[(3,3-Difluorocyclobutyl)methoxy]-2,3-dihydro-1H-inden-1-one2×

Product 1

HCID 86706719HCID 86706719, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 6-((3,3-difluorocyclobutyl)methoxy)-2,3-dihydro-1H-inden-1-one (Intermediate 11, 7.0 g, 27.8 mmol) and methyl acrylate (5.51 mL, 61.1 mmol) in 2-Me THF (6 mL) was cooled to 0° C. and potassium tert-butoxide (3.74 g, 33.3 mmol) was added in portions. After stirring for 2 h at r.t., water (9 mL) and potassium hydroxide (1.56 g, 27.8 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, providing 3.51 g, 37% yield of the title compound. 1H NMR (500 MHz, CDCl3) ppm 1.80-1.91 (m, 2H) 2.17-2.26 (m, 2H) 2.39-2.57 (m, 4H) 2.58-2.82 (m, 5H) 3.16 (s, 2H) 4.05 (d, 2H) 7.20 (d, 1H) 7.25 (dd, 1H) 7.40 (d, 1H); MS (ES+) m/z 335 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-f9c4f4a3f0844f769418a161ae1b674b
Source dataset
uspto-grants-2015_04
Patent number
US09000185B2

Reaction notes

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