Reacción #438653

Ecuación de reacción

NaOAc

NaCNBH3

aldehyde

3-(2,4-Difluoro-Benzyl)-3-Formyl-Piperazine-1-Carboxylic Acid Tert-Butyl Ester

MgSO4

methyl amine

→

3-(2,4-Difluoro-Benzyl)-3-Methylaminomethyl-Piperazine-1-Carboxylic Acid Tert-Butyl Ester

Disolventes

MeOH

DME

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcl(M+1)+ 354)
2. 2
   FiltraciónThe mixture was filtered through Celite®
3. 3
   Concentraciónthe filtrate was concentrated
4. 4
   Lavadowashed with 1N NaOH and brine solutions
5. 5
   SecadoThe organic phase was dried over MgSO4
6. 6
   Concentraciónconcentrated
7. 7
   OtroPurification by flash chromatography (SiO2 gel, 3:1:0.2. EtOAc:Hexane:EtOH)

Procedimiento

To a solution of the aldehyde of Example 198, Step A (340 mg, 1 mmol) in dry DME (10 mL) was added about 250 mg MgSO4 followed by methyl amine (1 mL of a 2.0M solution in MeOH, 2 equiv). The reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcl(M+1)+ 354). Once imine formation was complete, NaOAc (820 mg, 10 mmol) and NaCNBH3 (248 mg, 4 mmol) were added and the mixture was stirred at room temperature for 1 h. The mixture was filtered through Celite® and the filtrate was concentrated. The resulting residue was taken up in EtOAc (25 mL) and washed with 1N NaOH and brine solutions, respectively. The organic phase was dried over MgSO4 and concentrated to deliver the crude amine (360 mg). Purification by flash chromatography (SiO2 gel, 3:1:0.2. EtOAc:Hexane:EtOH) delivered 210 mg (59%) of the diamine of Example 198, Step B: +APcl MS (M+1)+ 356, (M−tBu+1)+ 300, (M−Boc+1)+ 256; 1H NMR=400 MHz (CDCl3) δ: 7.21 (m, 1H), 6.81 (m, 2H), 2.51 (br s, 3 H), 1.42 (s, 9H).

Fuente