Methyl chloroformate → Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-[(methoxycarbonyl)thio]-6-(trifluoromethyl)-3-pyridinecarboxylate

HRID 1007235Notes

Reaction equation

HRID 1007235 reaction equation
[F:1][CH:2]([F:22])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:6]([SH:17])=[C:5]([C:18]([F:21])([F:20])[F:19])[N:4]=1.Cl[C:24]([O:26][CH3:27])=[O:25].C(N(CC)CC)C>C1COCC1>[F:22][CH:2]([F:1])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:6]([S:17][C:24]([O:26][CH3:27])=[O:25])=[C:5]([C:18]([F:21])([F:20])[F:19])[N:4]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 9974711Methyl 2-(difluoromethyl)-4-isobutyl-5-mercapto-6-(trifluoromethyl)-3-pyridinecarboxylate

Product 1

HCID 22668810Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-[(methoxycarbonyl)thio]-6-(trifluoromethyl)-3-pyridinecarboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3.05 g (0.0089 mol) of product of example 1 and 0.094 g (0.01 mol) of methyl chloroformate in 25 mL dry THF was added 1.16 g (0.012 mol) of triethylamine dropwise at room temperature. After stirring for 30 min, the solvent was evaporated under reduced pressure. The residue was diluted with 100 mL of water and extracted with ether (3×50 mL). The combined organic layers were washed with water, dried (MgSO4) and evaporated. Purification of the residue by preparative HPLC (5% ethyl acetate-hexane) gave 2.75 g (77%) of product as a yellow oil: nD25 1.5830.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. additionThe residue was diluted with 100 mL of water
  3. extractionextracted with ether (3×50 mL)
  4. washThe combined organic layers were washed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customPurification of the residue by preparative HPLC (5% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-227e2c56fc7840fe872762168c1bab43
Source dataset
uspto-grants-2004_09
Patent number
US06794396B2

Reaction notes

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