Boron trifluoride etherate → 6'-Bromo-5'-fluorospiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione

HRID 1468081Notes

Reaction equation

HRID 1468081 reaction equation
[CH2:1]=[C:2]([O:5][Si](C)(C)C)[CH:3]=[CH2:4].[Br:10][C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][C:16](=[CH2:21])[C:17]2=[O:20])=[CH:13][C:12]=1[F:22].B(F)(F)F.CCOCC>C(Cl)Cl>[Br:10][C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][C:16]3([CH2:4][CH2:3][C:2](=[O:5])[CH2:1][CH2:21]3)[C:17]2=[O:20])=[CH:13][C:12]=1[F:22]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 5546572-(Trimethylsiloxy)-1,3-butadieneHCID 867066926-Bromo-5-fluoro-2-methylene-2,3-dihydro-1H-inden-1-one2×

Product 1

HCID 867066936'-Bromo-5'-fluorospiro[cyclohexane-1,2'-indene]-1',4(3'H)-dioneYield 53.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) solution of (buta-1,3-dien-2-yloxy)trimethylsilane (1.86 mL, 10.6 mmol) in DCM (80 mL) was 6-bromo-5-fluoro-2-methylene-2,3-dihydro-1H-inden-1-one (Intermediate 5, 2.32 g, 9.62 mmol) added. Boron trifluoride diethyl etherate (0.594 mL, 4.81 mmol) was added at 0° C. The reaction was stirred for 30 min., and then quenched with MeOH (1.0 mL). The reaction mixture was acidified with aq. 2 M HCl solution, and extracted with DCM. The organic phase was washed with brine, dried over sodium sulfate and concentrated. The product was purified by flash column chromatography using a stepwise gradient of heptane/EtOAc (7:1-3.5:1-1:1), to give the title compound (1.60 g, 53% yield). 1H NMR (500 MHz, CDCl3) δ ppm 1.83-1.94 (m, 2 H) 2.17-2.27 (m, 2 H) 2.38-2.51 (m, 2 H) 2.72 (dt, 2 H) 3.18 (s, 2 H) 7.25 (d, 1 H) 8.01 (d, 1 H); MS (ES+) m/z 311,313 [M+H]+.

Workup

  1. additionadded
  2. customquenched with MeOH (1.0 mL)
  3. extractionextracted with DCM
  4. washThe organic phase was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-4bbb6cc9634a46e6bdb0a95a46331e47
Source dataset
uspto-grants-2015_04
Patent number
US09000183B2

Reaction notes

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