2,4,6-Trimethylpyridine → Methanesulfonic acid 2-(2-chloromethyl-phenyl)-ethyl ester

HRID 1418011Notes

Reaction equation

HRID 1418011 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH2:10][OH:11].N1C(C)=CC(C)=CC=1C.[Cl-:21].[Li+].[S:23](Cl)([CH3:26])(=[O:25])=[O:24]>CN(C)C=O>[Cl:21][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH2:10][O:11][S:23]([CH3:26])(=[O:25])=[O:24]

Participants

6

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 31297Methanesulfonyl chlorideHCID 2390242-[2-(Hydroxymethyl)phenyl]ethanolHCID 433294Lithium Chloride

Product 1

HCID 54328826Methanesulfonic acid 2-(2-chloromethyl-phenyl)-ethyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Mix 2-(2-hydroxymethyl-phenyl)-ethanol (12.0 g, 78.8 mmol) and collidine (23 mL, 0.17 mol) and treat with lithium chloride (7.35 g, 0.173 mmol) in dimethylformamide (125 mL). Cool in an ice bath and treat, by dropwise addition, with mesyl chloride (13.4 mL). Stir at 0° C. for 4 hours, partition between ice water (300 mL) and a 1:1 mixture of ether:pentane (2×400 mL). Wash the organic layer with a saturated solution of CuSO4 (2×200 mL), dry (MgSO4) and purify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate) to give the title compound as a pale yellow oil (8.8 g, 45%).

Workup

  1. temperatureCool in an ice bath
  2. custompartition between ice water (300 mL)
  3. additiona 1:1 mixture of ether
  4. washWash the organic layer with a saturated solution of CuSO4 (2×200 mL)
  5. dry with materialdry (MgSO4)
  6. custompurify by silica gel chromatography (2.5:1 hexane/ethyl acetate followed by 2:1 hexane/ethyl acetate followed by 3:2 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8990c8b157014e0791f6d967b57dd615
Source dataset
uspto-grants-1999_03
Patent number
US05880119

Reaction notes

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