Cyclobutylamine → HCID 18324817, compound

HRID 1250903Notes

Reaction equation

HRID 1250903 reaction equation
[CH:1]1([NH2:5])[CH2:4][CH2:3][CH2:2]1.C(N1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=2[CH3:22])C1=S)C=C>ClCCl>[Cl:21][C:19]1[CH:18]=[CH:17][C:16]([CH3:22])=[C:15]([NH:11][CH2:12][CH2:13][CH2:14][NH:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)[CH:20]=1

Participants

4

Reactant 2

HCID 75645CyclobutylamineHCID 9925710HCID 9925710, compound

Product 1

HCID 18324817HCID 18324817, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To neat cyclobutylamine (10.0 mL) was added the hydrobromide salt of Example 8, Step B in two equal portions (2×4.3 g) 15 minutes apart at ambient temperature. The mixture was heated at reflux under nitrogen for 30 minutes, then cooled and partitioned between dichloromethane and 1N sodium hydroxide The aqueous layer was extracted with dichloromethane, the combined extracts were dried over sodium sulfate and concentrated in vacuo to give a brown oil. The crude material was dissolved in dichloromethane and absorbed onto a column of Merck-60 flash silica gel. Elution with a solvent gradient (from 98:2 dichloromethane-methanol to 80:20 dichloromethane-methanol containing 0.2% ammonium hydroxide) gave the title compound (3.7 g, 58.5%) as a brown solid, which was used as such in the next step.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under nitrogen for 30 minutes
  3. temperaturecooled
  4. custompartitioned between dichloromethane and 1N sodium hydroxide The aqueous layer
  5. extractionwas extracted with dichloromethane
  6. dry with materialthe combined extracts were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. customabsorbed onto a column of Merck-60 flash silica gel
  10. washElution with a solvent gradient (from 98:2 dichloromethane-methanol to 80:20 dichloromethane-methanol containing 0.2% ammonium hydroxide)

Sources & evidence

ORD record
ord-0f445250b10949eeb8d5f3bf07a39039
Source dataset
uspto-grants-2002_01
Patent number
US06340687B1

Reaction notes

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