Isobutyl chloroformate → HCID 86676204, compound

HRID 1426427Notes

Reaction equation

HRID 1426427 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:16]2[C@@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][C@H:9]1[C:17](O)=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)OCC(C)C.[NH2:28][C:29]1[CH:33]=[C:32]([Br:34])[S:31][C:30]=1[C:35]([NH2:37])=[O:36].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[Br:34][C:32]1[S:31][C:30]([C:35](=[O:36])[NH2:37])=[C:29]([NH:28][C:17]([C@@H:9]2[CH2:10][C@H:11]3[C@H:16]([CH2:15][CH2:14][CH2:13][CH2:12]3)[N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:18])[CH:33]=1

Participants

8

Reactant 4

HCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 2755991(2S,3aS,7aS)-1-(tert-Butoxycarbonyl)octahydro-1H-indole-2-carboxylic acidHCID 219758623-Amino-5-bromothiophene-2-carboxamide

Product 1

HCID 86676204HCID 86676204, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,3aS,7aS)-1-(tert-butoxycarbonyl)octahydro-1H-indole-2-carboxylic acid (638 mg) and triethylamine (0.392 mL) in tetrahydrofuran (5 mL) was added 2-methylpropyl chlorocarbonate (0.324 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. Thereafter, to the reaction system was added a solution of 3-amino-5-bromothiophene-2-carboxamide (250 mg) produced in Example 1, step D, in tetrahydrofuran (5 mL), and the mixture was stirred at 60° C. for 26 hr. Ethyl acetate (20 mL) and aqueous sodium hydrogen carbonate (10 mL) were added to the reaction mixture, and the separated aqueous layer was extracted with ethyl acetate (5 mL). The combined organic layers were washed with brine (5 mL) and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the object fraction was concentrated under reduced pressure to give the title compound (345 mg) as a pale-yellow amorphous solid.

Workup

  1. extractionthe separated aqueous layer was extracted with ethyl acetate (5 mL)
  2. washThe combined organic layers were washed with brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationInsoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  7. concentrationthe object fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-c7500308e29046baa5a9a360c95879f5
Source dataset
uspto-grants-2015_01
Patent number
US08933069B2

Reaction notes

Loading…