Hydrochloric Acid → HCID 15767135, compound

HRID 487854Notes

Reaction equation

HRID 487854 reaction equation
[Mg].II.Br[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[F:10][CH:11]([F:32])[C:12]1[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:15]([CH:26]=[O:27])=[C:14]([C:28]([F:31])([F:30])[F:29])[N:13]=1.Cl>CCOCC.O>[F:32][CH:11]([F:10])[C:12]1[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:15]([CH:26]([OH:27])[C:5]2[S:6][CH:7]=[CH:8][CH:9]=2)=[C:14]([C:28]([F:31])([F:29])[F:30])[N:13]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 807IodineHCID 138512-BromothiopheneHCID 5462224MagnesiumHCID 15107640Methyl 2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)6-(trifluoromethyl)-3-pyridinecarboxylate

Product 1

HCID 15767135HCID 15767135, compoundYield 77.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×

Procedure

This example illustrates the preparation of Compound Number 53. To a suspension of magnesium (1.4 g, 58 mmol) in anhydrous ether (40 mL) containing several iodine crystals was added dropwise a solution of 2-bromothiophene (10 g, 62 mmol) in anhydrous ether (20 mL). The reaction was exothermic; the mixture was stirred at ambient temperature for 1.5 h. The resulting Grignard reagent was cooled to 0°-5° C. and a solution of methyl 2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (6.8 g, 20 mmol) in anhydrous ether (20 mL) was added. The mixture was stirred for 2 h, poured into iced water, and acidified with conc. HCl. The organic layer was separated, washed with water and brine, dried (MgSO4), and conc. The residue was eluted on a silica gel column with 15% ethyl acetate/cyclohexane to yield 6.6 g of methyl 2-(difluoromethyl)-5-(hydroxy-2-thienylmethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate, a 77.6 % yield. m.p. 78°-88° C.

Workup

  1. customthe preparation of Compound Number 53
  2. stirringThe mixture was stirred for 2 h
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. washconc. The residue was eluted on a silica gel column with 15% ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-1ce2185d8434497bbeb8dc4a7fd5e371
Source dataset
uspto-grants-1994_03
Patent number
US05298479

Reaction notes

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