Formaldehyde → 7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-2-amine

HRID 1425567Notes

Reaction equation

HRID 1425567 reaction equation
[F:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:23]=[C:22]2[C:14]([C:15]3[CH:16]=[CH:17][C:18]([NH2:24])=[CH:19][C:20]=3[NH:21]2)=[CH:13][CH:12]=1.[CH2:25]=O.C[O-].[Na+].[BH4-].[Na+]>CO>[F:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:23]=[C:22]2[C:14]([C:15]3[CH:16]=[CH:17][C:18]([NH:24][CH3:25])=[CH:19][C:20]=3[NH:21]2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 582252137-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-amine

Product 1

HCID 592829957-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-2-amineYield 56.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-amine (95 mg, 0.28 mmol), paraformaldehyde (43 mg, 1.43 mmol), and NaOMe (492 mg, 25% MeOH solution, 2.3 mmol) in 8 mL of MeOH was heated at reflux for 1.5 h under Ar atmosphere and cooled to rt. To this mixture was added NaBH4 (54 mg, 1.43 mmol) and the mixture was heated at reflux for 2 h. After cooling to rt, the mixture was quenched onto ice. It was extracted with ether (3×30 mL) and the combined organic phase was dried over MgSO4 and concentrated. The crude product was purified with chromatography (hexane/EtOAc) to afford 7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-2-amine (AD-CB-003P-WZ0141) as a light-brown solid (55 mg, 56%). 1H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.77 (t, J=8.8 Hz, 2H), 6.78 (dd, J=8.0, 2.0 Hz, 1H), 6.77 (s, 1H), 6.53 (dd, J=8.4, 2.0 Hz, 1H), 6.46 (s, 1H), 4.62 9 m, 1H), 4.50 (m, 1H), 4.13 (t, J=5.2 Hz, 2H), 3.85 (t, J=5.2 Hz, 2H), 3.83 (s, 1H), 3.79-3.67 (m, 6H), 2.87 (s, 3H); MS (ESI) m/z 347 (M+H+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h under Ar atmosphere
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 2 h
  5. temperatureAfter cooling to rt
  6. customthe mixture was quenched onto ice
  7. extractionIt was extracted with ether (3×30 mL)
  8. dry with materialthe combined organic phase was dried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified with chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-9b77d7df4c6e4358bcdcb237d6848ba0
Source dataset
uspto-grants-2015_01
Patent number
US08932557B2

Reaction notes

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