Dimethyl Sulfide → 1-[2,4-Dihydroxy-3-(trifluoromethyl)phenyl]-2-methylpropan-1-one

HRID 2355266Notes

Reaction equation

HRID 2355266 reaction equation
C([O:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[C:13]([O:19]CC2C=CC=CC=2)[CH:12]=[CH:11][C:10]=1[C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])C1C=CC=CC=1.CSC.CS(O)(=O)=O>>[OH:8][C:9]1[C:14]([C:15]([F:16])([F:17])[F:18])=[C:13]([OH:19])[CH:12]=[CH:11][C:10]=1[C:27](=[O:31])[CH:28]([CH3:29])[CH3:30]

Participants

4

Reactant 3

HCID 1068Dimethyl SulfideHCID 6395Methanesulfonic AcidHCID 67176641HCID 67176641, compound

Product 1

HCID 534139691-[2,4-Dihydroxy-3-(trifluoromethyl)phenyl]-2-methylpropan-1-oneYield 69.2%

Conditions

Temperature
33 °C

Procedure

Stir 1-(2,4-bis-benzyloxy-3-trifluoromethyl-phenyl)-2-methyl-propan-1-one (1460 g, 3.07 mol) in dimethyl sulfide (8 L, 108.81 mol), treat with methanesulfonic acid (2.5 L, 38.13 mol), then gently reflux overnight. Cool mixture to 33° C. and treat with cracked ice (˜6 Kg) at such a rate as to keep the mixture below reflux. Transfer mixture to a separatory funnel, separate layers, and extract water layer with ethyl acetate (6 L). Wash organic layers with water (4 L), saturated sodium chloride solution (4 L), dry with magnesium sulfate, filter, and evaporate to a brown solid. Re-crystallize the solid from toluene (4 L) to afford 527 g of 1-(2,4-dihydroxy-3-trifluoromethyl-phenyl)-2-methyl-propan-1-one as a tan solid (3 crops). The filtrate is concentrated to 380 g of a black gritty oil and filtered through a pad of silica gel to provide 216 g of a yellow solid, which is re-crystallized from toluene to afford 69 g of additional material. All lots are combined to provide the title compound (596 g, 78% yield): HPLC Rt=4.98 min; 1H NMR (DMSO-d6) δ 14.15 (s, 1H), 11.70 (s, 1H), 8.06 (d, J=8.0 Hz, 1H), 6.57 (d, J=8.0 Hz, 1H), 3.62 (hept, J=8.0 Hz, 1H), 1.11 (d, J=8.0 Hz, 6H); 19F NMR (DMSO-d6) δ-54.50; MS (m/z): 249.0 (M+1).

Workup

  1. customgently reflux overnight
  2. temperaturebelow reflux
  3. customTransfer mixture to a separatory funnel, separate layers
  4. extractionextract water layer with ethyl acetate (6 L)
  5. dry with materialWash organic layers with water (4 L), saturated sodium chloride solution (4 L), dry with magnesium sulfate
  6. filtrationfilter
  7. customevaporate to a brown solid

Sources & evidence

ORD record
ord-e747c58216084823a97496a220e5be56
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

Loading…