Water → Methyl 4-(4-hydroxy-3,5-diisopropylphenyl)-4-oxobutanoate

HRID 1056478Notes

Reaction equation

HRID 1056478 reaction equation
[CH3:1][CH:2]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([CH:11]([CH3:13])[CH3:12])[C:9]=1[OH:10])[CH3:3].Cl[C:15](=[O:22])[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19].O>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[OH:10][C:9]1[C:4]([CH:2]([CH3:1])[CH3:3])=[CH:5][C:6]([C:15](=[O:22])[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[CH:7][C:8]=1[CH:11]([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 962WaterHCID 4943PropofolHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl ester

Product 1

HCID 19967177Methyl 4-(4-hydroxy-3,5-diisopropylphenyl)-4-oxobutanoateYield 39%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Propofol 5 (1.78 g, 10.0 mmol) and methyl 4-chloro-4-oxobutyrate (4.5 g, 25 mmol) were dissolved in methylene chloride (350 mL), the reaction mixture was cooled to −78° C. and titanium (IV) chloride (5.7 g, 30 mmol) was added drop-wise. The reaction mixture was stirred for 2 h at −78° C., allowed to warm up to room temperature and stirred overnight. The reaction mixture was then poured into water (300 mL), the organic phase was washed sequentially with saturated sodium bicarbonate solution, water and brine, and the solution dried over anhydrous magnesium sulfate. The product was purified by column chromatography on silica gel using hexane and hexane-ethyl acetate (4:1) step-gradient as an eluent to produce pure 6 (1.14 g, 39%) as a slightly yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.75 (s, 2H), 5.84 (s, 1H), 3.72 (s, 3H), 3.32 (t, J=6.8 Hz, 2H), 3.20 (septet, J=6.9 Hz, 2H), 2.76 (t, J=6.8 Hz, 2H), 1.28 (d, J=6.9 Hz, 12H). 13C NMR (100.61 MHz, CDCl3): δ 196.81, 173.35, 154.40, 133.27, 129.05, 123.97, 51.41, 32.59, 27.82, 26.79, 22.18. HRMS (m/z): [M+H]+ calcd. for C17H24O5 293.1747. found 293.1759.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred overnight
  3. washthe organic phase was washed sequentially with saturated sodium bicarbonate solution, water and brine
  4. dry with materialthe solution dried over anhydrous magnesium sulfate
  5. customThe product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-803105fac2be4798b0626dcbd4312acb
Source dataset
uspto-grants-2016_07
Patent number
US09399145B2

Reaction notes

Loading…