Dichloromethane → (S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide

HRID 883170Notes

Reaction equation

HRID 883170 reaction equation
O=C1CC([O:8][C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)CCO1.[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28](Br)=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C1(C)C=CC=CC=1.C(OCC)(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28]([N:12]2[CH2:13][C@@H:9]([OH:8])[CH2:10][C:11]2=[O:14])=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamideHCID 68495162(4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one

Product 1

HCID 24801838(S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamideYield 53%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one (0.036 g, 0.19 mmol), N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.050 g, 0.16 mmol), cesium carbonate (0.079 g, 0.24 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.003 g, 0.003 mmol) and xantphos (0.004 g, 0.006 mmol) in anhydrous toluene (3 mL) was subjected to microwave irradiation at 80° C. for 20 min. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (4 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in ethanol and a catalytic amount of pyridinium p-toluenesulfonate was added to the solution. The reaction mixture was heated at 50° C. for 6 hours and concentrated in vacuo. The residue was dissolved in dichloromethane (15 mL) and washed with water (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained white solid was washed with diethyl ether (25 mL) and dried in air to afford the title compound (0.028 g, 53%): mp 203-204° C. (diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.60 (t, J=6.0 Hz, 1H), 7.33-7.17 (m, 5H), 5.46 (d, J=3.8 Hz, 1H), 4.47-4.41 (m, 1H), 4.35 (d, J=6.0 Hz, 2H), 4.12-4.04 (m, 1H), 3.93-3.85 (m, 1H), 3.00-2.90 (m, 1H), 2.48 (s, 3H), 2.42-2.33 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 173.3, 162.1, 155.9, 140.0, 128.7, 127.7, 127.2, 119.4, 63.6, 57.0, 43.1, 41.7, 17.5; MS (ES+) m/z 332.2 (M+1).

Workup

  1. customirradiation at 80° C. for 20 min
  2. washwashed with water (4 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in ethanol
  7. additiona catalytic amount of pyridinium p-toluenesulfonate was added to the solution
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in dichloromethane (15 mL)
  10. washwashed with water (5 mL)
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. washThe obtained white solid was washed with diethyl ether (25 mL)
  15. customdried in air

Sources & evidence

ORD record
ord-990c3c50656042f8aa410aad2d8bb536
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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