Diisopropylethylamine → HCID 68503233, compound

HRID 2387640Notes

Reaction equation

HRID 2387640 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][C:21]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:25]([C:26](=[S:28])[NH2:27])[N:24]=[C:23]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[S:22]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:44]1[C:49](=O)[CH2:48][CH2:47][N:46]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:45]1.CCN(C(C)C)C(C)C>C(O)C>[Si:1]([O:18][CH2:19][CH2:20][C:21]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:25]([C:26]2[S:28][C:44]3[CH2:45][N:46]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:48][C:49]=3[N:27]=2)[N:24]=[C:23]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[S:22]1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 106839701-tert-Butyloxycarbonyl-3-bromo-4-oxopiperidine2×HCID 86608783HCID 86608783, compound

Product 1

HCID 68503233HCID 68503233, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-(2-(tert-butyldiphenylsilyloxy)ethyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazole-3(2H)-carbothio amide (0.500 g, 0.809 mmol) in 20 mL of ethanol was added tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (0.338 g, 1.21 mmol) followed by DIEA (0.423 mL, 2.43 mmol). The mixture was allowed to stir overnight at reflux then treated with tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (200 mg) and stirred at reflux for a further 3 hours. The cooled mixture was partitioned between saturated NaHCO3 solution (50 mL) and EtOAc (50 mL) and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phases were washed with brine (50 mL) dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (5-10% ethyl acetate/hexanes) to afford the desired product as a viscous yellow oil, 0.412 g, 64%.

Workup

  1. temperatureat reflux
  2. stirringstirred
  3. temperatureat reflux for a further 3 hours
  4. customThe cooled mixture was partitioned between saturated NaHCO3 solution (50 mL) and EtOAc (50 mL)
  5. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washThe combined organic phases were washed with brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (5-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4bedbb60e207489b9ba616d59403ba58
Source dataset
uspto-grants-2012_09
Patent number
US08268871B2

Reaction notes

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