Ethyl chloroformate → HCID 11392958, compound

HRID 853048Notes

Reaction equation

HRID 853048 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[C:16]([O:20][C:21]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][C:30]=2[CH2:32][CH3:33])[CH:25]=[CH:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].Cl[C:35]([O:37][CH2:38][CH3:39])=[O:36].[Cl-].[NH4+]>O1CCCC1>[CH3:39][CH2:38][O:37][C:35]([C:24]1[N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[C:31]2[C:26]([CH:25]=1)=[CH:27][CH:28]=[CH:29][C:30]=2[CH2:32][CH3:33])=[O:36]

Participants

7

Reactant 5

HCID 10928Ethyl chloroformateHCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 11149257HCID 11149257, compoundHCID 178418339Butyllithium

Product 1

HCID 11392958HCID 11392958, compoundYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2,2,6,6-Tetramethylpiperidine (2.21 g, 15.6 mmol) was dissolved in 30 mL tetrahydrofuran and cooled down to −75° C. n-Butyllithium (9 mL, 14.3 mmol, 1.6M solution in n-hexane) was added while maintaining the temperature below −70° C. After 50 min., a solution of 3.2 g (13.0 mmol) 7-ethyl-indole-1-carboxylic acid tert-butyl ester in 15 mL tetrahydrofuran was added and the temperature again kept below −70° C. After 50 min., ethyl chloroformate (1.4 mL (14.3 mmol) was added and the temperature was allowed to rise to −50° C. After 1 h the reaction mixture was poured into 30 mL saturated aq. ammonium chloride solution and the phases separated. The aqueous phase was extracted once with 50 mL diethyl ether and the combined organic extractions were washed successively with saturated aq. ammonium chloride solution and water, dried over magnesium sulfate, filtered and evaporated. The crude reaction product was flash-chromatographed over silica gel (0.030–0.060 mm) with n-hexane/tert-butyl methyl ether (39/1) as eluant to give the product as a yellow oil (2.3 g, 56.2%). EI-MS: m/e=317.2 ([M])

Workup

  1. additionwas added
  2. temperaturewhile maintaining the temperature below −70° C
  3. customthe temperature again kept below −70° C
  4. waitAfter 50 min.
  5. customto rise to −50° C
  6. customthe phases separated
  7. extractionThe aqueous phase was extracted once with 50 mL diethyl ether
  8. extractionthe combined organic extractions
  9. washwere washed successively with saturated aq. ammonium chloride solution and water
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe crude reaction product
  14. customwas flash-chromatographed over silica gel (0.030–0.060 mm) with n-hexane/tert-butyl methyl ether (39/1) as eluant

Sources & evidence

ORD record
ord-14e3f72a6bff419d91b8d8b42a40ffdb
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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