Methanol → 3-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzonitrile

HRID 1818463Notes

Reaction equation

HRID 1818463 reaction equation
[C:1]([C:4]1[CH:33]=[CH:32][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([O:25]C3CCCCO3)[C:17]3[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=3)[C:20]#[N:21])=[CH:12][CH:11]=2)=[C:6]([CH2:34][CH2:35][CH3:36])[C:5]=1[OH:37])(=[O:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO.ClCCl>C(OCC)(=O)C>[C:1]([C:4]1[CH:33]=[CH:32][C:7]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([CH:16]([OH:25])[C:17]3[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=3)[C:20]#[N:21])=[CH:14][CH:15]=2)=[C:6]([CH2:34][CH2:35][CH3:36])[C:5]=1[OH:37])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 666996043-[[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile

Product 1

HCID 666995493-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzonitrileYield 93%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Stir a mixture of 3-[[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (13.4 g, 26.88 mmol), p-toluenesulfonic acid monohydrate (5.1 g, 26.88 mmol), methanol (100 mL), dichloromethane (50 mL), and ethyl acetate (50 mL) at room temperature for an hour. Concentrate the reaction mixture, dilute with ethyl acetate (150 mL) and wash with water (2×100 mL). Dry the organic phase over magnesium sulfate, filter, and concentrate. Dilute the residue with 5:1 hexanes:dichloromethane (50 mL), cool to 0° C. and filter. Collect a second and third crop to give the title compound (10.3 g, 93%), as a white solid. LCMS 416 M+1. The following compounds are prepared essentially as described in Preparation 33.

Workup

  1. concentrationConcentrate the reaction mixture
  2. additiondilute with ethyl acetate (150 mL)
  3. washwash with water (2×100 mL)
  4. dry with materialDry the organic phase over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. additionDilute the residue with 5:1 hexanes
  8. filtrationfilter
  9. customCollect a second and third crop

Sources & evidence

ORD record
ord-d8f965496b3247a08808c0698666ada3
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

Loading…