Isobutylene → HCID 86653600, compound

HRID 1892008Notes

Reaction equation

HRID 1892008 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:20])[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH2:11][CH:10]([CH2:18][OH:19])[CH2:9]2)=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].O.[C:26]1([CH3:36])[CH:31]=CC(S(O)(=O)=O)=C[CH:27]=1.CC(=C)C>ClCCl>[C:26]([O:19][CH2:18][CH:10]1[CH2:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:21]([F:22])([F:23])[F:24])[CH:4]=2)([CH3:20])[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH2:11]1)([CH3:36])([CH3:31])[CH3:27]

Participants

5

Reactant 3

HCID 8255Isobutylene2×HCID 521998p-Toluenesulfonic acid monohydrateHCID 86653598HCID 86653598, compound

Product 1

HCID 86653600HCID 86653600, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl (4RS,6RS)-6-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-6-methylcyclohex-1-enecarboxylate (Example 7, Step 9; 36.7 mg, 0.101 mmol) in dichloromethane (2 mL) was placed in a sealable tube, treated with p-toluenesulfonic acid hydrate (96 mg, 0.506 mmol) and cooled on dry ice. Liquid isobutylene (1-2 mL) was added, the tube was sealed and the mixture was stirred at rt for 72 h. After this time, the tube was cooled and unsealed, and the isobutylene was allowed to evaporate. The resulting mixture was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate and concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 5-25% ethyl acetate-hexane, to provide methyl (4RS,6RS)-4-(tert-butoxymethyl)-6-(4-chloro-3-(trifluoro-methyl)phenyl)-6-methylcyclohex-1-enecarboxylate (22 mg, 52%). Mass spectrum m/z 436.0 (M+NH4+). 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J=2.2 Hz, 1 H), 7.37 (d, J=8.6 Hz, 1 H), 7.30 (dd, J=8.4, 2.2 Hz, 1 H), 7.27 (dd, J=5.5, 2.9 Hz, 1 H), 3.64 (s, 3 H), 3.15 (dd, J=8.8, 4.4 Hz, 1 H), 3.07 (dd, J=8.6, 6.4 Hz, 1 H), 2.47 (m, 1 H), 1.96 (m, 1 H), 1.69 (m, 1 H), 1.64 (s, 3 H), 1.54 (m, 2 H), 1.11 (s, 9 H).

Workup

  1. temperaturecooled on dry ice
  2. customthe tube was sealed
  3. temperatureAfter this time, the tube was cooled
  4. customto evaporate
  5. additionThe resulting mixture was diluted with dichloromethane
  6. washwashed with saturated aqueous sodium bicarbonate
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto yield a residue
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with 5-25% ethyl acetate-hexane

Sources & evidence

ORD record
ord-a796b1ba17c741e6a75b0dc440737504
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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