2-Bromothiazole → HCID 66657144, compound

HRID 660109Notes

Reaction equation

HRID 660109 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:23]1[S:24][CH:25]=[CH:26][N:27]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.F[B-](F)(F)F.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([N:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[C:23]2[S:24][CH:25]=[CH:26][N:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 764302-BromothiazoleHCID 23676156Sodium t-butoxideHCID 44558591Tri-t-butylphosphine fluoroborateHCID 66657279HCID 66657279, compound

Product 1

HCID 66657144HCID 66657144, compoundYield 31.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a 150 ml of toluene solution containing 20.0 g of 3(S)-(3,4-dichlorophenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester (60.4 mmol) and 15.0 g of 2-bromothiazole (91.5 mmol) were added 1.86 g of tri-tert-butylphosphine•tetrafluoroborate (6.4 mmol), 2.88 g of tris(dibenzylideneacetone)dipalladium (3.15 mmol) and 11.6 g of sodium tert-butoxide (120 mmol). The mixture was heated under reflux under a nitrogen atmosphere for 9 hours. The reaction solution was cooled to room temperature and filtered using Celite. Water was added to the filtrate, and extraction with ethyl acetate was conducted. After drying over sodium sulfate and concentration under reduced pressure, the residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 7.94 g of yellow powdery 3(S)-[(3,4-dichlorophenyl)-thiazol-2-ylamino]pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux under a nitrogen atmosphere for 9 hours
  3. filtrationfiltered
  4. additionWater was added to the filtrate, and extraction with ethyl acetate
  5. dry with materialAfter drying over sodium sulfate and concentration under reduced pressure
  6. customthe residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)
  7. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-c296ddd1778a4098bbdf692fbddc493d
Source dataset
uspto-grants-2011_12
Patent number
US08084442B2

Reaction notes

Loading…