Chlorotrimethylsilane → HCID 67139408, compound

Temperature

50 °C

Onto zinc foil (99.9% Aldrich 35, 602-6, 775 mg, 11.85 mmol) cut in small pieces is added DMF (freshly distilled from CaH2 under argon, 4.5 mL) and 1,2-dibromoethane (0.033 mL, 0.38 mmol) under argon. The mixture is heated at 50° C. for 10 min, then allowed to cool and trimethylsilyl chloride (0.19 mL, 0.153 mmol) is added. The reaction is stirred for 25 min and a solution of (R)-2-t-butoxycarbonylamino-3-iodo-propionic acid benzyl ester (Fluka, 2.18 g, 5.37 mmol) in DMF (10 mL) is added. After 15 min, the mixture is decanted into a solution of the title A compound, 5-(4-iodo-phenyl)-2-(4-methoxy-benzyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (1.75 g, 3.82 mmol), tri-o-tolylphosphine (232.5 mg, 0.764 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (175 mg, 0.191 mmol) in DMF (13 mL). After stirring for 1.5 h, the resulting reaction mixture is poured onto a mixture of saturated aqueous ammonium chloride (200 mL) and water (200 mL) and extracted with EtOAc (2×250 mL). The organic solution is washed with water (1×200 mL) and brine (1×200 mL), then filtered through celite to removed a strong gray precipitate. The filtrate is dried over anhydrous Na2SO4, filtered and concentrated to give a dark red brown oil. This is chromatographed on a 110 g silica gel RediSep column (Isco, Inc.) with a 30 mL/min gradient elution of 0:100 (EtOAc:CH2Cl2) to 10:90 over 25 min. Fractions containing product are combined and concentrated to yield (S)-2-t-butoxycarbonylamino-3-(4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionic acid benzyl ester as a white solid after tritruration with Et2O: [M+NH4]+=627.0, [M−HCO2]−=654.1.

1. distillationfreshly distilled from CaH2 under argon
2. temperatureto cool
3. waitAfter 15 min
4. stirringAfter stirring for 1.5 h
5. customthe resulting reaction mixture
6. extractionextracted with EtOAc (2×250 mL)
7. washThe organic solution is washed with water (1×200 mL) and brine (1×200 mL)
8. filtrationfiltered through celite
9. customto removed a strong gray precipitate
10. dry with materialThe filtrate is dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customto give a dark red brown oil
14. customThis is chromatographed on a 110 g silica gel RediSep column (Isco, Inc.) with a 30 mL/min gradient elution of 0:100 (EtOAc:CH2Cl2) to 10:90 over 25 min
15. additionFractions containing product
16. concentrationconcentrated

ORD record

ord-c6ceb7b6ba174eb0b8c359047c26faae

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07291635B2