Citric Acid → Methyl 3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl]benzoate

HRID 602154Notes

Reaction equation

HRID 602154 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:14]([OH:16])=O)=[C:11]([CH3:13])[N:12]=2)=[CH:4][CH:3]=1.O.O[N:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2N=N1.Cl.C[N:30](C)CCCN=C=NCC.CN1CC[O:44][CH2:43]C1.[C:47](O)(=O)[CH2:48][C:49]([CH2:54][C:55](O)=O)(C(O)=O)O.CN(C)[CH:62]=[O:63]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([C:14]([NH:30][CH:54]3[CH2:49][CH2:48][CH2:47][N:19]([C:23]4[CH:22]=[C:27]([CH:26]=[CH:25][CH:24]=4)[C:43]([O:63][CH3:62])=[O:44])[CH2:55]3)=[O:16])=[C:11]([CH3:13])[N:12]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 6

HCID 311Citric AcidHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27686792-(4-Chlorophenyl)-4-methyl-1,3-thiazole-5-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 57497929Methyl 3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl]benzoate

Procedure

Methyl 3-[3-(tert-butoxycarbonylamino)piperidin-1-yl]benzoate (154 mg, 0.461 mmol) was dissolved in a 10% hydrogen chloride/methanol solution (10 mL) and the solution was stirred at room temperature for 1 hour. Concentration of the reaction mixture resulted in 135 mg of a brown amorphous product. This product (118 mg), along with 2-(4-chlorophenyl)-4-methylthiazole-5-carboxylic acid (111 mg, 0.436 mmol) and 1-hydroxybenzotriazole monohydrate (80.1 mg, 0.523 mmol), was dissolved in N,N-dimethylformamide (5 mL). While this solution was chilled in an ice bath, 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide hydrochloride (100 mg, 0.523 mmol) and N-methylmorpholine (0.115 mL, 1.05 mmol) were added. The mixture was stirred at room temperature for 6 hours and 5% aqueous citric acid was added. The resulting mixture was extracted with ethyl acetate and the extract washed sequentially with a saturated aqueous sodium bicarbonate solution and brine. The washed product was dried over magnesium sulfate and the solvent was evaporated. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=5:1->1:1) gave 112 mg of the desired compound as a pale yellow powder.

Workup

  1. temperatureWhile this solution was chilled in an ice bath
  2. extractionThe resulting mixture was extracted with ethyl acetate
  3. washthe extract washed sequentially with a saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialThe washed product was dried over magnesium sulfate
  5. customthe solvent was evaporated
  6. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=5:1->1:1)

Sources & evidence

ORD record
ord-e941f07306104286a417eb694e93c30d
Source dataset
uspto-grants-2011_03
Patent number
US07902367B2

Reaction notes

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