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

HRID 1770878Notes

Reaction equation

HRID 1770878 reaction equation
[C:1]([O:5]C)(=O)[CH:2]=[CH2:3].[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][CH2:13][C:14]2=[O:17])=[CH:10][CH:9]=1.[CH3:18][C:19](C)([O-])C.[K+].[OH-].[K+]>C1COCC1.CC(C)([O-])C.[K+]>[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][C:13]3([CH2:3][CH2:2][C:1](=[O:5])[CH2:19][CH2:18]3)[C:14]2=[O:17])=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 7294Methyl Acrylate3×HCID 14797Potassium HydroxideHCID 1397781-Indanone, 6-bromo-HCID 23665647Potassium tert-butoxide

Product 1

HCID 581972056'-Bromospiro[cyclohexane-1,2'-indene]-1',4(3'H)-dioneYield 62%

Reagents, catalysts & solvents 2

HCID 23665647Potassium tert-butoxideCatalyst3×HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
20 °C

Procedure

Methyl acrylate (6.6 L, 73 mol) was charged gradually in three equal portions (each 2.2 L, 24.6 mol) to a mixture of 6-bromo-1-indanone (8.00 kg, 37.9 mol), THF (16 L) and potassium tert-butoxide (210 g, 1.87 mol) at approximately 20-30° C. Additional potassium tert-butoxide (86 g, 0.77 mol), dissolved in THF (0.39 L), was charged after the first portion of methyl acrylate. More potassium tert-butoxide (86 g, 0.77 mol), dissolved in THF (0.39 L), was charged after the second portion of methyl acrylate. Further potassium tert-butoxide (4.64 kg, 41.3 mol) solution in THF (21 L) was then charged gradually at approximately 20-30° C. Solvent (21.5 L) was distilled off at approximately 65° C. and then a mixture of water (49 L) and 50%. aq KOH (2.3 L, 30 mol) was added over approximately 10 min. at below 60° C. The reaction was held at 60° C. for approximately 6 h., then cooled to 20° C. over 1 h. and then filtered after holding at 20° C. for approximately 12 h. The solids were washed with a mixture of water (8 L) and THF (4 L), and then dried to give the title compound (7.47 kg, at 92% w/w NMR assay, 23.4 mol, 62% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.78-1.84 (m, 2H), 1.95 (td, 2H), 2.32-2.38 (m, 2H), 2.51-2.59 (m, 2H), 3.27 (s, 2H), 7.60 (d, 1H), 7.81 (m, 1H), 7.89 (m, 1H).

Workup

  1. distillationSolvent (21.5 L) was distilled off at approximately 65° C.
  2. additiona mixture of water (49 L) and 50%
  3. filtrationfiltered
  4. waitafter holding at 20° C. for approximately 12 h
  5. washThe solids were washed with a mixture of water (8 L) and THF (4 L)
  6. customdried

Sources & evidence

ORD record
ord-79ae655aabae4aadb54194de4b5e016e
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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