Methanol → 3'-(Chloromethyl)-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl

HRID 1848780Notes

Reaction equation

HRID 1848780 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:5]=[C:4]([CH3:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23]O)[CH:18]=1.P(Cl)(Cl)([Cl:27])=O.O.CO>CN(C)C=O>[Cl:27][CH2:23][C:19]1[CH:18]=[C:17]([C:3]2[C:2]([CH3:1])=[CH:7][C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])=[CH:5][C:4]=2[CH3:16])[CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962Water2×HCID 24813Phosphorus oxychlorideHCID 593425562',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)(1,1'-biphenyl)-3-methanol

Product 1

HCID 862228633'-(Chloromethyl)-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenylYield 92.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To {2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol (2.40 g) was added N,N-dimethylformamide (7.2 mL), and the mixture was stirred for 20 min. The N,N-dimethylformamide solution was added dropwise at 25° C. to a separately prepared solution of phosphorus oxychloride (1.37 g) in N,N-dimethylformamide (4.8 mL). After stirring at 25° C. for 1 hr, water (2.4 mL), then methanol (12 mL), and water (2.4 mL) were added dropwise. Seed crystal was added, and the mixture was stirred at room temperature for 1 hr and at 10° C. or below for 1 hr. The precipitated crystals were collected by filtration, washed with water (24 mL), and dried at 50° C. under reduced pressure to give 3′-chloromethyl-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl (2.33 g).

Workup

  1. stirringAfter stirring at 25° C. for 1 hr
  2. additionSeed crystal was added
  3. stirringthe mixture was stirred at room temperature for 1 hr and at 10° C. or below for 1 hr
  4. filtrationThe precipitated crystals were collected by filtration
  5. washwashed with water (24 mL)
  6. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-0ed4d347604c41e58660bbe8e515bb06
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

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