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

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.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in CH2Cl2
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in CH2Cl2 (30 mL)
5. stirringThe reaction was stirred for 12 h
6. custompartitioned between EtOAc and sat. NH4Cl
7. washThe organic phase was washed with sat. NaHCO3 and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash chromatography

ORD-Eintrag

ord-b13095700ecc48d396d9f66f47704806

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07863317B2