Ammonia → 2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide

HRID 1269525Notes

Reaction equation

HRID 1269525 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([C:19]3[S:23][C:22]([C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=4)=[N:21][C:20]=3[CH3:34])=[O:18])[CH2:12]2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.C[N:42](C)C=O.N>C(Cl)Cl.C(OCC)C.C1COCC1>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([C:19]3[S:23][C:22]([C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:26][CH:25]=4)=[N:21][C:20]=3[CH3:34])=[O:18])[CH2:12]2)=[CH:7][C:3]=1[C:4]([NH2:42])=[O:6]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 10254929(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid

Product 1

HCID 103907432-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamideYield 72%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid (Example 9-1; 1.026 g, 2.10 mmol) was dissolved in 20 mL CH2Cl2 and treated with oxalyl chloride (0.22 mL, 2.52 mmol) and 10 mL of dimethyl formamide. The mixture was allowed to stir for 1 h until all solids had dissolved. 10 mL of THF saturated with ammonia was added slowly. A thick white precipitate formed. The slurry was stirred for 20 min then diluted with diethyl ether (100 mL), washed with 100 mL of each of H2O, 0.2 N aqueous HCl, saturated aqueous NaHCO3, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 50% ethyl acetate/hexanes to yield 740 mg (72%) of the desired 2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide as a clear oil.

Workup

  1. dissolutionhad dissolved
  2. customA thick white precipitate formed
  3. stirringThe slurry was stirred for 20 min
  4. washwashed with 100 mL of each of H2O, 0.2 N aqueous HCl, saturated aqueous NaHCO3, and brine
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f5987667c9e3487da85dd426f6112fb1
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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