Reacción #337987

Ecuación de reacción

N, N-diisopropylethylamine

HOBt

N-Boc methionine

BOP

TFA

[1S,2S]-[1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-carbamic acid tert-butyl ester

→

[2S,3S]-[2-[(2S)-(2-tert-butoxycarbonylamino-4-methylsulfanyl-butyrylamino)]-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester

Rendimiento 78.2%

Disolventes

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónconcentrated in vacuo
2. 2
   workup.DISSOLUTIONThe residue was dissolved in CH2Cl2
3. 3
   Concentraciónconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in CH2Cl2 (30 mL)
5. 5
   workup.STIRRINGThe reaction was stirred for 12 h
6. 6
   Otropartitioned between EtOAc and sat. NH4Cl
7. 7
   LavadoThe organic phase was washed with sat. NaHCO3 and brine
8. 8
   Secadodried (Na2SO4)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated in vacuo
11. 11
    OtroThe residue was purified by flash chromatography

Procedimiento

A solution of [1S,2S]-[1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-carbamic acid tert-butyl ester (1.19 g, 3.29 mmol, prepared as described in WO PCT 0250019) was dissolved in CH2Cl2 (20 mL) and treated with TFA (10 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in CH2Cl2 and concentrated in vacuo; this procedure was repeated. The residue was dissolved in CH2Cl2 (30 mL). The resultant solution was charged sequentially with N, N-diisopropylethylamine (2.3 mL, 13.2 mmol), HOBt (466 mg, 3.45 mmol), N-Boc methionine (820 mg, 3.29 mmol), and BOP (1.53 g, 3.45 mmol). The reaction was stirred for 12 h and partitioned between EtOAc and sat. NH4Cl. The organic phase was washed with sat. NaHCO3 and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford [2S,3S]-[2-[(2S)-(2-tert-butoxycarbonylamino-4-methylsulfanyl-butyrylamino)]-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (1.27 g, 78% yield). MS found: (M+Na)+=516.3.

Fuente