tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamate → tert-Butyl 3-((4-(4-fluorophenoxy)benzylamino)methyl)benzylcarbamate

HRID 1889620Notes

Reaction equation

HRID 1889620 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=1)[CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11].[F:18][C:19]1[CH:33]=[CH:32][C:22]([O:23][C:24]2[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=2)=[CH:21][CH:20]=1.[Na]>C(Cl)Cl>[F:18][C:19]1[CH:33]=[CH:32][C:22]([O:23][C:24]2[CH:31]=[CH:30][C:27]([CH2:28][NH:1][CH2:2][C:3]3[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=3)[CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[CH:26][CH:25]=2)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 2756043tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamateHCID 38568024-(4-Fluorophenoxy)benzaldehydeHCID 5360545Sodium

Product 1

HCID 66616559tert-Butyl 3-((4-(4-fluorophenoxy)benzylamino)methyl)benzylcarbamateYield 60.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-(aminomethyl)benzylcarbamate (0.70 g, 2.94 mmol) and 4-(4-fluorophenoxy)benzaldehyde (0.6 g, 2.78 mmol) in CH2Cl2 (15 mL) was stirred at rt under nitrogen for 40 min, and then treated with sodium triacetoxyhydroborate (1.24 g, 5.83 mmol). The resulting mixture was stirred at rt. for 3 h. The reaction mixture was concentrated and the residue was partitioned between saturated NaHCO3 solution and ethyl acetate. The organic layer (clear solution) was washed with brine, dried over MgSO4. The filtrate was concentrated and the residue was dissolved in CH2Cl2 and ethyl acetate. The solution was loaded into solid sample cartridge, vacuum dried. The sample was purified by silica gel flash chromatography. Elution with 0-30% of ethyl acetate in CH2Cl2 gave the desired product as viscous oil (0.73 g, 59%). 1H NMR (DMSO-d6): δ 7.33-7.28 (m, 2H), 7.24-7.19 (m, 5H), 7.13 (m, 1H), 7.08-7.02 (m, 2H), 6.95 (m, 2H), 4.12 (m, 2H), 3.76 (s, 4H), 1.39 (s, 9H); MS (ESI): (M+H)+=437.3.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between saturated NaHCO3 solution and ethyl acetate
  3. washThe organic layer (clear solution) was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationThe filtrate was concentrated
  6. dissolutionthe residue was dissolved in CH2Cl2
  7. customdried
  8. customThe sample was purified by silica gel flash chromatography
  9. washElution with 0-30% of ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-cb29a33444164406b7ca049ea5f8acf6
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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