Hydrochloric Acid → HCID 178497592, compound

HRID 865653Notes

Reaction equation

HRID 865653 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][NH:9][C:10]=2[CH:11]=[CH:12][CH:13]=1)=[O:4].C([Mg]Br)C.[C:18]([NH:28][CH2:29][C@H:30]1[CH2:35][CH2:34][C@H:33]([C:36](Cl)=[O:37])[CH2:32][CH2:31]1)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].[NH4+].[Cl-].Cl>C(Cl)Cl.[Cl-].[Cl-].[Zn+2].C(Cl)Cl.CO>[CH3:1][O:2][C:3]([C:5]1[C:6]2[C:7]([C:36]([C@H:33]3[CH2:32][CH2:31][C@H:30]([CH2:29][NH:28][C:18]([O:20][CH2:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)=[O:19])[CH2:35][CH2:34]3)=[O:37])=[CH:8][NH:9][C:10]=2[CH:11]=[CH:12][CH:13]=1)=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 2733668methyl 1H-indole-4-carboxylateHCID 178418443HCID 178418443, compoundHCID 178523385HCID 178523385, compound

Product 1

HCID 178497592HCID 178497592, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of indole-4-carboxylic acid methyl ester (2.33 g, 13.3 mmol) in CH2Cl2 (25 mL) was added ethylmagnesium bromide (3M in ether, 4.4 mL, 13.2 mmol). The reaction mixture was stirred for five minutes and ZnCl2 (1M in ether, 40 mL, 40 mmol) was added and the cloudy, brown suspension was stirred for 15 minutes. A solution of trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride (4.36 g, 14.1 mmol), prepared as in step 2, in CH2Cl2 (20 mL) was added and the reaction mixture was stirred for three hours. The reaction mixture was poured into a separatory funnel containing saturated aqueous NH4Cl which left a green-brown gum. The gum was broken up by trituration with aqueous 1M HCl and CH2Cl2 /methanol and added to the separatory funnel. The layers were separated and the organic phase was washed with saturated aqueous NaHCO3, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica gel (1%, then 3% methanol/CH2Cl2) gave 3-[(trans-4-(N-carbobenzyloxy)aminomethylcyclohex-1-yl)carbonyl]indole-4-carboxylic acid methyl ester (2.83 g, 48%) as a tan foam.

Workup

  1. stirringthe cloudy, brown suspension was stirred for 15 minutes
  2. stirringthe reaction mixture was stirred for three hours
  3. additionThe reaction mixture was poured into a separatory funnel
  4. waitleft a green-brown gum
  5. additionadded to the separatory funnel
  6. customThe layers were separated
  7. washthe organic phase was washed with saturated aqueous NaHCO3
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a96666e4e9b144e0925f7ee5c5e280fc
Source dataset
uspto-grants-1996_10
Patent number
US05567711

Reaction notes

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