Methanesulfonic Acid → 1-Methyl-2-[3-(methyloxy)phenyl]ethyl methanesulfonate

HRID 1992809Notes

Reaction equation

HRID 1992809 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH:10]([OH:12])[CH3:11])[CH:6]=[CH:7][CH:8]=1.CCN(CC)CC.[CH3:20][S:21](O)(=[O:23])=[O:22]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:20][S:21]([O:12][CH:10]([CH3:11])[CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)(=[O:23])=[O:22]

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 124998521-(3-Methoxyphenyl)propan-2-ol

Product 1

HCID 866166351-Methyl-2-[3-(methyloxy)phenyl]ethyl methanesulfonateYield 98.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a cold solution (5° C.) of 1-[3-(methyloxy)phenyl]-2-propanol (1) (75 g, 0.45 mol) in CH2Cl2 (500 mL) were added Et3N (100 mL, 0.72 mol) and DMAP (2.75 g, 22.5 mmol). Methanesulfonic acid (52 mL, 0.675 mol) was added slowly (drop-wise) to the above reaction mixture at that temperature over a period of 40 min. The resultant mixture was stirred between 5° C. and 10° C. for 8 h under N2. The reaction mixture was washed with H2O (3×150 mL), brine (1×100 mL), dried (Na2SO4) and concentrated under reduced pressure to afford the crude product which was passed through a pad of silica to afford 108 g (98%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.24 and 7.20 (dd, J1=15.2 Hz, J2=3.8 Hz, 1H), 6.81-6.76 (m, 3H), 4.87 (sextet, J=6.00 Hz, 1H), 3.77 (s, 3H), 2.96 and 2.92 (dd, J1=14.0 Hz, J2=8.0 Hz, 1H), 2.87 and 2.84 (dd, J1=14.0 Hz, J2=5.6, Hz, 1H), 2.54 (s, 3H), 1.44 (d, J=6.4 Hz, 3H).

Workup

  1. washThe reaction mixture was washed with H2O (3×150 mL), brine (1×100 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customto afford the crude product which

Sources & evidence

ORD record
ord-d475fbe92ae94ab9aeeeefb11f4f6464
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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