Acetic Acid → HCID 66707028, compound

HRID 911389Notes

Reaction equation

HRID 911389 reaction equation
[CH2:1]([NH:8][C:9]1[C:19]2[CH2:18][CH2:17][N:16](C([O:22][C:23]([CH3:26])(C)C)=O)[CH2:15][CH2:14][C:13]=2[CH:12]=[CH:11][C:10]=1[Cl:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=[O:29].[C:30]([BH3-])#N.[Na+].[C:34]([OH:37])(=[O:36])[CH3:35]>C(#N)C.CO.O>[C:23]([OH:22])(=[O:29])[CH2:26][CH2:35][C:34]([OH:37])=[O:36].[Cl:27][C:10]1[CH:11]=[CH:12][C:13]2[CH2:14][CH2:15][NH:16][CH2:17][CH2:18][C:19]=2[C:9]=1[N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH3:30]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 66706976HCID 66706976, compound

Product 1

HCID 66707028HCID 66707028, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dissolve 6-benzylamino-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (50 mg, 0.11 mmol) in acetonitrile (3 mL) and add a solution of formaldehyde in water (37%, 85 μL, 0.97 mmol) followed by sodium cyanoborohydride (16.5 mg, 0.26 mmol). Heat the solution to reflux 1 h, cool to ambient temperature, add glacial acetic acid (0.25 mL) and stir 72 h. Pour the mixture into water (100 mL) containing methanol (1 mL), extract with DCM (3×20 mL), wash the organic extracts with brine, dry over MgSO4, filter and concentrate in vacuo. Dissolve the resulting residue in DCM (5 mL), and add trifluoroacetic acid (2 mL). Stir for 2 h at ambient temperature and evaporate the solvent. Purify by SCX chromatography. Use a method similar to the General Procedure 2-1 to give the title compound (45 mg, 95%). MS (ES+) m/z: 301 (M+H)+.

Workup

  1. temperatureHeat the solution
  2. temperatureto reflux 1 h
  3. extractionextract with DCM (3×20 mL)
  4. washwash the organic extracts with brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. dissolutionDissolve the resulting residue in DCM (5 mL)
  9. additionadd trifluoroacetic acid (2 mL)
  10. stirringStir for 2 h at ambient temperature
  11. customevaporate the solvent
  12. customPurify by SCX chromatography

Sources & evidence

ORD record
ord-31e5b1c7fa174bb39a51e2b4fea7454f
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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