Triethylamine → 4-[2-Methyl-4-(tetrahydro-pyran-2-yloxy)-6-trifluoromethanesulfonyloxy-phenyl]-4-oxo-butyric acid methyl ester

HRID 1798039Notes

Reaction equation

HRID 1798039 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[CH:10][C:9]=1[OH:21])=[O:7].[CH3:23]CN(CC)CC.[O:30](S(C(F)(F)F)(=O)=O)[S:31]([C:34]([F:37])([F:36])[F:35])(=O)=[O:32]>ClCCl.O>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][C:6]([C:8]1[C:9]([O:21][S:31]([C:34]([F:37])([F:36])[F:35])(=[O:32])=[O:30])=[CH:10][C:11]([O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[CH:12][C:13]=1[CH3:23])=[O:7]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59525512methyl 4-(2-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)phenyl)-4-oxobutanoate

Product 1

HCID 873258704-[2-Methyl-4-(tetrahydro-pyran-2-yloxy)-6-trifluoromethanesulfonyloxy-phenyl]-4-oxo-butyric acid methyl esterYield 63.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-[2-hydroxy-4-(tetrahydro-pyran-2-yloxy)-phenyl]-4-oxo-butyric acid methyl ester (2.87 g, 8.91 mmol) and Et3N (3.71 mL, 26.73 mmol) in dichloromethane (30 mL) was added Tf2O (2.30 mL, 13.37 mmol) at −78° C. The mixture was stirred at −78° C. for 2 hours, diluted with H2O and extracted with dichloromethane. The organic extracts were washed with brine, dried and concentrated in vacuo. The residue was dissolved in Hexane-EtOAc(4:1), filtered through a plug of silica gel and filtrate was concentrated to give 4-[2-methyl-4-(tetrahydro-pyran-2-yloxy)-6-trifluoromethanesulfonyloxy-phenyl]-4-oxo-butyric acid methyl ester (2.56 g, 63%). 1HNMR (400 MHz, CDCl3): 6.95 (s, 1H), 6.90 (s, 1H), 5.45 (s, 1H), 3.82 (m, 1H), 3.77 (s, 3H), 3.65 (m, 1H), 3.10 (t, J=6.5 Hz, 2H), 2.75 (t, J=6.5 Hz, 2H), 2.30 (s, 3H), 2.05-1.50 (m, 6H).

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic extracts were washed with brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in Hexane-EtOAc(4:1)
  6. filtrationfiltered through a plug of silica gel and filtrate
  7. concentrationwas concentrated

Sources & evidence

ORD record
ord-aa037e7eb6f0426588a7c8ec271e7fe1
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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