Tetrahydrofuran → HCID 15037588, compound

HRID 1007244Notes

Reaction equation

HRID 1007244 reaction equation
[F:1][CH:2]([F:31])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([NH:13][CH:14]([CH3:16])[CH3:15])[C:6]([C:17]([O:19]CC2C=CC=CC=2)=[O:18])=[C:5]([C:27]([F:30])([F:29])[F:28])[N:4]=1.C1COCC1>CO.[Pd]>[F:31][CH:2]([F:1])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([NH:13][CH:14]([CH3:16])[CH3:15])[C:6]([C:17]([OH:19])=[O:18])=[C:5]([C:27]([F:30])([F:28])[F:29])[N:4]=1

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 14013904HCID 14013904, compound

Product 1

HCID 15037588HCID 15037588, compoundYield 101.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 46.27 g (0.1 mol) of 3-methyl 5-benzyl 2-(difluoromethyl)-4-(1-methylethylamino)-6-(trifluoromethyl)-3,5-pyridinedicarboxylate (example 181 of U.S. Pat. No. 4,698,093) in 1.2 L of a 1:5 mixture of THF in methanol was hydrogenated using catalytic 5% Pd/C under 50 lb of hydrogen pressure for 48 h. The reaction mixture was filtered through Celite and concentrated in vacuo to give 36 g of 3-methyl 5-hydrogen 2-(difluoromethyl)-4-(1-methylethylamino)-6-(trifluoromethyl)-3,5-pyridinedicarboxylate. To a mixture of 34.7 g of this monoacid in 400 ml of carbon tetrachloride was added 23 g (0.11 mol) of phosphorus pentachloride. The reaction mixture was stirred at room temperature until HCl evolution stopped. The reaction mixture was held at reflux for 20 min and concentrated in vacuo affording 38.04 g of monoacid chloride as a yellow oil. A portion (3.75 g 0.01 mol) of this oil and 1.7 g (0.01 mol) of triethyl phosphite was heated to 160° C. and then cooled. The resulting oil was purified by HPLC (25% EtOAc in hexane) affording 2.09 g of (44%) of product as a thick yellow oil.

Workup

  1. customfor 48 h
  2. filtrationThe reaction mixture was filtered through Celite
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5ce26d9c4eae488382512cdfea47a3bc
Source dataset
uspto-grants-2004_09
Patent number
US06794396B2

Reaction notes

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