Thiazole → Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoate

HRID 14288

Reaction equation

HRID 14288 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH2:11]([N:14]([CH2:28][CH2:29][CH3:30])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25](I)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:12][CH3:13]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:28]([N:14]([CH2:11][CH2:12][CH3:13])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:29][CH3:30]

Participants

7

Reactant 3

HCID 9256ThiazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

Product 1

HCID 21086169Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoateYield 99.1%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a −78° C. solution of thiazole (1.2 g) in THF (25 mL) was added n-butyl lithium (1.6 M in hexanes, 10 mL). The mixture was stirred for 30 min and then allowed to warm to 0° C. in an ice/water bath. Zinc chloride (1M in ethyl ether, 40 mL) was added and the mixture was stirred for 1 h, at which time methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate (5.1 g) in THF (20 mL) was added, followed by Pd(PPh3)4 (palladium tetrakis triphenylphosphine) (0.68 g). The mixture was then heated at 80° C. for 2 h, at which time it was allowed to cool and partitioned between ethyl acetate and water. The organic layers were washed with brine, dried (magnesium sulfate), and concentrated. The residue was chromatographed on silica gel using ethyl acetate/heptane (50/50) to give 4.5 g of methyl 3-[(dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoate.

Workup

  1. additionwas added
  2. temperatureThe mixture was then heated at 80° C. for 2 h, at which time it
  3. temperatureto cool
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layers were washed with brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-8c15277c81ef4130b983117271cafa80
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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