Triethylamine → Ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutane carboxylate

HRID 1436380Notes

Reaction equation

HRID 1436380 reaction equation
C(N(CC)CC)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=O)[CH2:16][S:17][C:18]#[N:19])=[CH:11][CH:10]=1.Cl.[NH2:22][C:23]1([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:26][CH2:25][CH2:24]1>C(O)C>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]=[C:18]([NH:22][C:23]3([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:26][CH2:25][CH2:24]3)[S:17][CH:16]=2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2449684'-Bromophenacyl thiocyanateHCID 16217503Ethyl 1-aminocyclobutane-1-carboxylate hydrochloride

Product 1

HCID 86618583Ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutane carboxylateYield 12.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
68 °C

Procedure

Triethylamine (3.30 mL, 23.7 mmol) was added under nitrogen to a mixture of 2-(4-bromophenyl)-2-oxoethyl thiocyanate (5.50 g, 21.6 mmol), prepared in step 1 of Example 1, and ethyl 1-aminocyclobutanecarboxylate hydrochloride (4.24 g, 23.6 mmol) in 130 mL of absolute ethanol. The mixture was then stirred at 68° C. overnight. The reaction was concentrated under reduced pressure to remove the ethanol. The residue was partitioned between ethyl acetate and water. The aqueous layer was made basic by the addition of 2 N NaOH. The organic layer was separated, washed two times with water, dried (MgSO4), filtered and the solvent removed under reduced pressure. Purification of the residue on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge) using a linear gradient of 45% methylene chloride in hexane to 100% methylene chloride as the eluent gave ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutane carboxylate (1.0 g, 12%) as a brown oil, MS (ESI) m/z 381 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customto remove the ethanol
  3. customThe residue was partitioned between ethyl acetate and water
  4. additionThe aqueous layer was made basic by the addition of 2 N NaOH
  5. customThe organic layer was separated
  6. washwashed two times with water
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customPurification of the residue on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge)

Sources & evidence

ORD record
ord-d732f1ca94374cd3891108fbd00fd048
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

Loading…