Potassium Phosphate, Tribasic → Methyl 1-(4-phenylthiazol-2-yl)pyrrolidine-3-carboxylate

HRID 874944Notes

Reaction equation

HRID 874944 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.[CH3:13][O:14][C:15]([CH:17]1[CH2:21][CH2:20][NH:19][CH2:18]1)=[O:16].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:7]1([C:5]2[N:6]=[C:2]([N:19]3[CH2:20][CH2:21][CH:17]([C:15]([O:14][CH3:13])=[O:16])[CH2:18]3)[S:3][CH:4]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 4114360Methyl Pyrrolidine-3-carboxylateHCID 99211062-Bromo-4-phenyl-1,3-thiazole

Product 1

HCID 67323747Methyl 1-(4-phenylthiazol-2-yl)pyrrolidine-3-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-4-phenylthiazole (300 mg, 1.25 mmol) and pyrrolidine-3-carboxylic acid methyl ester (177 mg, 1.37 mmol) and potassium phosphate (290 mg, 1.37 mmol) in dry toluene (5 mL) were taken in a sealed tube and purged argon gas for 10 min. A catalytic amount of tri-tert-butylphosphine (12 mg, 0.06 mmol) was added, followed by palladium acetate (15 mg, 0.06 mmol), and the reaction mixture was heated to 80° C. for 10 h. The reaction mixture was then filtered through Celite and the clear filtrate was concentrated under reduced pressure to get the crude product which was purified by column chromatography (silica 60-120 mesh, eluant 15-18% EtOAc in petroleum ether) to get methyl 1-(4-phenylthiazol-2-yl)pyrrolidine-3-carboxylate (75 mg, yield 73%). 1H NMR (300 MHz, CDCl3) δ 7.87-7.83 (m, 2H), 7.44-7.31 (m, 4H), 3.88-3.78 (m, 2H), 3.75 (s, 3H), 3.70-3.67 (m, 1H), 3.61-3.55 (m, 1H), 3.32-3.23 (m, 1H), 2.41-2.32 (m, 2H). MS (ESI) m/z: Calculated for C16H16N2O2S: 288.09. found: 289.2 (M+H)+

Workup

  1. customwere taken in a sealed tube
  2. custompurged argon gas for 10 min
  3. filtrationThe reaction mixture was then filtered through Celite
  4. concentrationthe clear filtrate was concentrated under reduced pressure
  5. customto get the crude product which
  6. customwas purified by column chromatography (silica 60-120 mesh, eluant 15-18% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-25a054d8ac304921a587c696fbf8589e
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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