Hydrochloric Acid → HCID 59828864, compound

HRID 1191038Notes

Reaction equation

HRID 1191038 reaction equation
C(OC([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]([CH:20]2[CH2:22][CH2:21]2)=[O:19])=[CH:12][CH:11]=1)=O)(C)(C)C.Cl>CCOC(C)=O.CO>[CH:20]1([C:18]([NH:17][CH2:16][C:13]2[CH:12]=[CH:11][C:10]([CH2:9][NH2:8])=[CH:15][CH:14]=2)=[O:19])[CH2:21][CH2:22]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 59828879HCID 59828879, compound

Product 1

HCID 59828864HCID 59828864, compoundYield 77.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve N-(tert-butoxycarbonyl)-4-[(cyclopropanecarbonyl-amino)-methyl]-benzylamine (529 mg, 1.74 mmol) in EtOAc (20 mL) and MeOH (15 mL). Bubble hydrogen chloride through the solution for 15 min, and stir the mixture overnight at room temperature. Concentrate the mixture in vacuo and dissolve the resulting solid in water. Adjust the pH to 9-11 with 20% aqueous K2CO3 (w/w %) and extract three times with chloroform/iso-propanol (3:1). Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g, pre-packed cartridge) eluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 4:1 over 5 min, 1:1 over 10 min, 1:3; 50 mL/min) to obtain the desired intermediate (275 mg, 77%). MS (APCI+) m/z: 188 (M-NH3+H)+.

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. dissolutiondissolve the resulting solid in water
  3. extractionextract three times with chloroform/iso-propanol (3:1)
  4. dry with materialDry the combined organic extracts over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by chromatography on silica gel (40 g, pre-packed cartridge)
  8. washeluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 4:1 over 5 min, 1:1 over 10 min, 1:3; 50 mL/min)

Sources & evidence

ORD record
ord-f03a34d7205a4981a77f4e00f5a746e9
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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