Dimethyl Sulfoxide → 2-(3,5-Dichloropyrid-4-yl)-1-(3-cyclopentyloxy-6-fluoro-4-methoxyphenyl)ethanone

HRID 1092816Notes

Reaction equation

HRID 1092816 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:13]=[N:14][CH:15]=[C:16]([Cl:36])[C:17]=1[CH2:18][CH:19]([C:21]1[C:26]([F:27])=[CH:25][C:24]([O:28][CH3:29])=[C:23]([O:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:22]=1)[OH:20].C(N(CC)CC)C>ClCCl.O>[Cl:36][C:16]1[CH:15]=[N:14][CH:13]=[C:12]([Cl:11])[C:17]=1[CH2:18][C:19]([C:21]1[C:26]([F:27])=[CH:25][C:24]([O:28][CH3:29])=[C:23]([O:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:22]=1)=[O:20]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 221459052-(3,5-Dichloropyrid-4-yl)-1-(3-cyclopentyloxy-6-fluoro-4-methoxyphenyl)ethanol

Product 1

HCID 221458102-(3,5-Dichloropyrid-4-yl)-1-(3-cyclopentyloxy-6-fluoro-4-methoxyphenyl)ethanoneYield 70.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of oxalyl chloride (0.05 mL) in dichloromethane (3 mL) is cooled to −60° C. and dimethylsulfoxide (1 mL) added. After stirring at this temperature for 0.25 hours, a solution of 2-(3,5-dichloropyrid-4-yl)-1-(3-cyclopentyloxy-6-fluoro-4-methoxyphenyl)ethanol (0.2 g) in dichloromethane (5 mL) is added dropwise. After stirring at −60° C. for 0.25 hours, triethylamine (0.33 mL) is added dropwise and the solution stirred for 0.25 hour at −60° C. and then at room temperature overnight. The solution is then poured into water (30 mL), extracted with ethyl acetate (3×50 mL) and the combined organic extracts washed with brine (30 mL), dried (magnesium sulfate), and concentrated to give a yellow-brown oil. The oil is subjected to mplc on silica gel, using petroleum ether:ethyl acetate (3:1 v/v) as eluent to give 2-(3,5-dichloropyrid-4-yl)-1-(3-cyclopentyloxy-6-fluoro-4-methoxyphenyl)ethanone (0.14 g). m.p. 115-116.5° C. [Elemental analysis: C, 57.7; H, 4.7; N, 3.5%; calculated: C, 57.3; H, 4.6; N, 3.5%].

Workup

  1. stirringAfter stirring at −60° C. for 0.25 hours
  2. stirringthe solution stirred for 0.25 hour at −60° C.
  3. customat room temperature
  4. customovernight
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washthe combined organic extracts washed with brine (30 mL)
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated
  9. customto give a yellow-brown oil

Sources & evidence

ORD record
ord-29827f5ac033484b9ba71cb8b595caf6
Source dataset
uspto-grants-2012_03
Patent number
US08129537B2

Reaction notes

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