4'-Fluorobiphenyl-4-carbaldehyde → tert-Butyl 3-(((4'-fluorobiphenyl-4-yl)methylamino)methyl)benzylcarbamate

HRID 1889677Notes

Reaction equation

HRID 1889677 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[NH2:16][CH2:17][C:18]1[CH:19]=[C:20]([CH:30]=[CH:31][CH:32]=1)[CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26].[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][NH:16][CH2:17][C:18]3[CH:19]=[C:20]([CH:30]=[CH:31][CH:32]=3)[CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 13925504'-Fluorobiphenyl-4-carbaldehydeHCID 2756043tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamateHCID 4311764Sodium borohydride

Product 1

HCID 58531402tert-Butyl 3-(((4'-fluorobiphenyl-4-yl)methylamino)methyl)benzylcarbamateYield 85.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

4′-Fluorobiphenyl-4-carbaldehyde (1.0 g, 5 mmol, 1.0 eq) and tert-butyl 3-(amino methyl)benzylcarbamate (1.18 g, 5 mmol, 1 eq) were dissolved in dry methanol under nitrogen and refluxed for 4 h. The reaction mass was cooled to 0° C. and sodium borohydride (570 mg, 15 mmol, 3 eq) was added portionwise at 0° C. over 20-30 minutes. The mixture was stirred for 1 h at 0° C. and then the reaction was quenched with 10% aq. sodium bicarbonate solution. The mixture was stirred at room temperature for 1 h. The resulting solution was completely evaporated under vacuum and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel (60-120) column chromatography using 5-10% methanol dichloromethane as the eluent to afford the desired compound (1.8 g, 85%) as a light yellow liquid. 1H NMR (400 MHz, DMSO-d6) δ 1.30-1.37 (d, 9H), 3.66-3.69 (d, 4H), 4.09-4.11 (d, 2H), 7.07-7.09 (d, 1H), 7.18-7.29 (m, 6H), 7.36-7.42 (m, 1H), 7.56-7.59 (m, 2H), 7.65-7.67 (d, 2H), 7.68-7.70 (m, 2H). MS (ESI): 421.0 (M+H)+.

Workup

  1. temperaturerefluxed for 4 h
  2. customthe reaction was quenched with 10% aq. sodium bicarbonate solution
  3. stirringThe mixture was stirred at room temperature for 1 h
  4. customThe resulting solution was completely evaporated under vacuum
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. customevaporated under reduced pressure
  8. customThe residue was purified by silica gel (60-120) column chromatography

Sources & evidence

ORD record
ord-ce66057c56d54259a7e15870cd1590fe
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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