Methanol → Acetic acid, 2-[4-(4-bromophenyl)-4-hydroxycyclohexylidene]-, methyl ester

HRID 881766Notes

Reaction equation

HRID 881766 reaction equation
[H-].[Na+].C[C:4](P(OC)(O)=O)([C:6]([O-:8])=[O:7])[CH3:5].[Br:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2([OH:28])[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1.[CH3:29]O>>[Br:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]23[O:28][C:5]([CH2:4][C:6]([O:8][CH3:29])=[O:7])([CH2:25][CH2:26]2)[CH2:23][CH2:22]3)=[CH:19][CH:20]=1.[Br:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2([OH:28])[CH2:26][CH2:25][C:24](=[CH:4][C:6]([O:8][CH3:29])=[O:7])[CH2:23][CH2:22]2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 53413272TrimethylphosphonoacetateHCID 67715663HCID 67715663, compound

Product 2

HCID 86700872HCID 86700872, compoundYield 12%HCID 86700873Acetic acid, 2-[4-(4-bromophenyl)-4-hydroxycyclohexylidene]-, methyl esterYield 63%

Procedure

To a solution of NaH (60% dispersion in mineral oil, 70 mg, 1.7 mmol) in methanol (6.7 mL) was added trimethylphosphonoacetate (0.23 mL, 1.6 mmol) and the reaction was let stir at rt for 30 min. To the reaction was added 4-(4-bromophenyl)-4-hydroxycyclohexanone (360 mg, 1.3 mmol) and the reaction was let stir at rt for 20 h. The resulting reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over MgSO4, filtered and concentrated by rotary evaporation in vacuo to afford 530 mg of a crude opaque oil. Purification of the crude material by column chromatography (25 g silica gel, 0-60% EtOAc:Hept, monitor 230 nm) afforded 51 mg (12%) of methyl 2-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)acetate as a colorless oil (ESI-MS m/z: 327.1 [M+H]+, retention time 1.56 min (condition E)) and 275 mg (63%) of the title compound as a colorless oil (ESI-MS m/z: n/a [M+H]+, retention time 1.42 min (condition E)). 1H NMR (400 MHz, DMSO-d6): δ ppm 1.71-1.93 (m, 4H), 2.19 (d, J=13.1 Hz, 1H), 2.29-2.44 (m, 1H), 2.66 (td, J=12.6, 4.7 Hz, 1H), 3.56-3.69 (m, 4H), 5.24 (s, 1H), 5.72 (s, 1H), 7.41-7.52 (m, 4H). 13C NMR (100 MHz, DMSO-d6): δ ppm 166.1, 162.5, 148.7, 130.6, 127.1, 119.3, 112.6, 70.8, 50.6, 38.7, 32.4, 24.5.

Workup

  1. stirringthe reaction was let stir at rt for 20 h
  2. customThe resulting reaction mixture
  3. customwas quenched with saturated aqueous ammonium chloride solution
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation in vacuo
  8. customto afford 530 mg of a crude opaque oil
  9. customPurification of the crude material by column chromatography (25 g silica gel, 0-60% EtOAc:Hept, monitor 230 nm)

Sources & evidence

ORD record
ord-722fafc44f284928aa38716c13d38e57
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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