Hydrochloric Acid → HCID 86675794, compound

HRID 239905Notes

Reaction equation

HRID 239905 reaction equation
[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].[C:6]([O:10][C:11]([NH:13][C:14]1[C:15]([CH3:29])=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([CH3:23])[C:18]([C:24](OCC)=[O:25])=[CH:17]2)=[O:12])([CH3:9])([CH3:8])[CH3:7].Cl.C(=O)([O-])O.[Na+]>C(O)C.C1COCC1.O>[OH:25][CH2:24][C:18]1[N:19]([CH3:23])[C:20]2[C:16]([CH:17]=1)=[C:15]([CH3:29])[C:14]([NH:13][C:11](=[O:12])[O:10][C:6]([CH3:7])([CH3:9])[CH3:8])=[CH:22][CH:21]=2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 70967919HCID 70967919, compound

Product 1

HCID 86675794HCID 86675794, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of calcium chloride (81 g) in ethanol (147 mL) was added sodium borohydride (6.93 g) at 5° C., and the mixture was stirred at the same temperature for 30 min. To the reaction mixture was added dropwise at 5° C. a solution of ethyl 5-[(tert-butoxycarbonyl)amino]-1,4-dimethyl-1H-indole-2-carboxylate (195 g) obtained in Reference Example 44 in THF (1.2 L), and the mixture was stirred at the same temperature for 30 min and at room temperature for 15 hr. While maintaining the reaction mixture at 20° C. or below, 1N hydrochloric acid (1.4 L) was added dropwise to adjust to pH 3, and water (1 L) and saturated aqueous sodium hydrogen carbonate (190 mL) were added. The organic solvent was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The precipitated solid was washed with ethyl acetate (200 mL) and petroleum ether (600 mL), and dried under reduced pressure to give the title compound (134 g, yield 79%) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at the same temperature for 30 min and at room temperature for 15 hr
  2. temperatureWhile maintaining the reaction mixture at 20° C. or below
  3. additionwere added
  4. customThe organic solvent was evaporated under reduced pressure
  5. extractionthe residual aqueous layer was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washThe precipitated solid was washed with ethyl acetate (200 mL) and petroleum ether (600 mL)
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-f032aabe7e704e5ebbb96d8bb22df5aa
Source dataset
uspto-grants-2014_02
Patent number
US08642770B2

Reaction notes

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