Triethylamine → Methyl 3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxycarbonylamino]piperidin-1-yl]benzoate

HRID 602190Notes

Reaction equation

HRID 602190 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([N:11]2[CH2:19][CH2:18][CH2:17][CH:13](C(O)=O)[CH2:12]2)[CH:8]=[CH:9][CH:10]=1)=[O:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.C([N:39]([CH2:42]C)CC)C.[Cl:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[S:52][C:53]([CH2:57][OH:58])=[C:54]([CH3:56])[N:55]=2)=[CH:47][CH:46]=1>C1C=CC=CC=1.O>[Cl:44][C:45]1[CH:46]=[CH:47][C:48]([C:51]2[S:52][C:53]([CH2:57][O:58][C:42]([NH:39][CH:13]3[CH2:17][CH2:18][CH2:19][N:11]([C:7]4[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=4)[C:3]([O:2][CH3:1])=[O:4])[CH2:12]3)=[O:27])=[C:54]([CH3:56])[N:55]=2)=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 27636922-(4-Chlorophenyl)-4-methyl-5-thiazolemethanolHCID 589926191-[3-(Methoxycarbonyl)phenyl]nipecotic acid

Product 1

HCID 58992614Methyl 3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxycarbonylamino]piperidin-1-yl]benzoateYield 52%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

1-[3-(Methoxycarbonyl)phenyl]nipecotic acid (105 mg, 0.400 mmol) was suspended in benzene (8 mL). To this suspension, diphenylphosphoryl azide (0.0948 mL, 0.440 mmol) and triethylamine (0.0615 mL, 0.440 mmol) were added and the mixture was stirred for 2 hours while being refluxed. Subsequently, 2-(4-chlorophenyl)-4-methylthiazol-5-yl methanol (105 mg, 0.440 mmol) and triethylamine (0.0615 mL, 0.440 mmol) were added and the mixture was further stirred for 6 hours while refluxed. Water was then added and the mixture was extracted with ethyl acetate. The extract washed sequentially with a saturated aqueous sodium bicarbonate solution and brine. This was followed by drying over magnesium sulfate and evaporation of the solvent. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=10:1->2:1) gave 103 mg (52%) of the desired compound as a colorless powder.

Workup

  1. temperaturewhile being refluxed
  2. stirringthe mixture was further stirred for 6 hours
  3. temperaturewhile refluxed
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract washed sequentially with a saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialby drying over magnesium sulfate and evaporation of the solvent
  7. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=10:1->2:1)

Sources & evidence

ORD record
ord-b42a8753ec3e42ccbddc3c7f6c4617f1
Source dataset
uspto-grants-2011_03
Patent number
US07902367B2

Reaction notes

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