Pyridine → Phenol, 3-chloro-5-methoxy-, 1-methanesulfonate

HRID 2264718Notes

Reaction equation

HRID 2264718 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1.N1C=CC=CC=1.CS([Cl:33])(=O)=O>ClCCl>[Cl:33][C:7]1[CH:6]=[C:5]([O:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 59596280HCID 59596280, compound

Product 1

HCID 57431691Phenol, 3-chloro-5-methoxy-, 1-methanesulfonateYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 0° C. solution of 3-chloro-5-methoxy-phenol (Scheme #4, K) (16.62 g, 104.80 mmol) and pyridine (12.8 mL, 157.20 mmol) in dichloromethane (150 mL) was added methanesulfonyl chloride (8.9 mL, 115.28 mmol). The reaction was warmed to room temperature and stirred 24 hours. The dichloromethane was removed under reduced pressure and the crude material partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was washed 1N hydrochloric acid (4×), aqueous saturated sodium chloride (1×), saturated potassium carbonate (3×), aqueous saturated sodium chloride (1×), dried over magnesium sulfate, and solvent removed under reduced pressure. The crude solid was crystallized overnight from dichloromethane (50 mL) and crystals filtered off, washed with dichloromethane, and placed under high vacuum to give the title compound (9.35 g, 38%). 1H NMR (300 MHz, DMSO-d6) δ 7.09 (t, J=2.0 Hz, 1 H), 7.05 (t, J=1.9 Hz, 1 H), 6.93 (t, J=2.1 Hz, 1 H), 3.82 (s, 3 H), 3.42 (s, 3 H); MS (APCI+) m/z 237 [M+1]+; tR=2.28 min.

Workup

  1. customThe dichloromethane was removed under reduced pressure
  2. customthe crude material partitioned between ethyl acetate and 1N hydrochloric acid
  3. washThe organic layer was washed 1N hydrochloric acid (4×), aqueous saturated sodium chloride (1×), saturated potassium carbonate (3×), aqueous saturated sodium chloride (1×)
  4. dry with materialdried over magnesium sulfate, and solvent
  5. customremoved under reduced pressure
  6. customThe crude solid was crystallized overnight from dichloromethane (50 mL) and crystals
  7. filtrationfiltered off
  8. washwashed with dichloromethane

Sources & evidence

ORD record
ord-679593d1eb784413a813906871a548a7
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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