Hexachloroethane → HCID 66823388, compound

HRID 1910077Notes

Reaction equation

HRID 1910077 reaction equation
[Li]C(C)(C)C.[CH3:6][C:7]([O:10][C:11]([N:13]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:14]1[C:19]2[C:20]([C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]4)=[CH:21][O:22][C:18]=2[C:17](I)=[CH:16][N:15]=1)=[O:12])([CH3:9])[CH3:8].[Cl:47]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[CH3:6][C:7]([O:10][C:11]([N:13]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:14]1[C:19]2[C:20]([C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]4)=[CH:21][O:22][C:18]=2[C:17]([Cl:47])=[CH:16][N:15]=1)=[O:12])([CH3:9])[CH3:8]

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 66823890HCID 66823890, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 66823388HCID 66823388, compoundYield 30.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

tBuLi (1.7 M in pentane) (0.59 mL, 1.003 mmol) was added dropwise to a solution of 1,1-dimethylethyl 5-[4-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-7-iodofuro[3,2-c]pyridin-3-yl]-2,3-dihydro-1H-indole-1-carboxylate (307 mg, 0.453 mmol) in THF (7 mL) at −78° C. under Nitrogen. The mixture was stirred at that temperature for 15 minutes, then a solution of hexachloroethane (217 mg, 0.917 mmol) in THF (3 mL) was added dropwise. The reaction was stirred and allowed to slowly warm from −78° C. to room temperature for 16 hours. The mixture was then quenched with saturated NH4Cl (25 mL), and extracted with ethyl acetate (2×20 mL). The extracts were washed with brine (1×20 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 40 g SiO2 [RediSep Gold column], 0%-25% EtOAc in hexanes gradient over 45 minutes). The second peak (1st big one) was collected to give 1,1-dimethylethyl 5-[4-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-7-chlorofuro[3,2-c]pyridin-3-yl]-2,3-dihydro-1H-indole-1-carboxylate (81 mg, 0.138 mmol, 30.5% yield) as a colorless oil. LC/MS (ES) m/z=586, 588 [M+H]+. The third peak to elute was also collected and found to be 1,1-dimethylethyl 5-[7-chloro-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)furo[3,2-c]pyridin-3-yl]-2,3-dihydro-1H-indole-1-carboxylate (33 mg, 0.068 mmol, 14.99% yield), also as a colorless oil. LC/MS (ES) m/z=486, 488 [M+H]+.

Workup

  1. stirringThe reaction was stirred
  2. temperatureto slowly warm from −78° C. to room temperature for 16 hours
  3. customThe mixture was then quenched with saturated NH4Cl (25 mL)
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. washThe extracts were washed with brine (1×20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (Analogix, 40 g SiO2 [RediSep Gold column], 0%-25% EtOAc in hexanes gradient over 45 minutes)
  10. customThe second peak (1st big one) was collected

Sources & evidence

ORD record
ord-d58937ebefab473b9af2be6d71a01294
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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