Chloroacetyl chloride → (S)-N-(2-bromo-9-(hydroxymethyl)-7-iodo-9H-xanthen-9-yl)-2-chloroacetamide

Temperature

0 °C

The (S)-(9-amino-2-bromo-7-iodo-9H-xanthen-9-yl)methanol (3.84 g, 8.89 mmol) was dissolved in THF (200 mL). The solution was cooled to 0° C., and TEA (1.425 mL, 10.22 mmol) and 2-chloroacetyl chloride (0.707 mL, 9.07 mmol) were added. The reaction was allowed to warm naturally to RT. After 14 h, the reaction was concentrated. The residue was taken up in aqueous 1 M Na2CO3 (50 mL) and the aqueous phase was extracted with 7.5% MeOH-DCM (3×133 mL). The organics were combined, washed with aqueous 1 M Na2CO3 (30 mL), dried over sodium sulfate and concentrated. The residue was dissolved in THF (100 mL) and aqueous 1 M Na2CO3 (15 mL) was added. The reaction was concentrated. The residue was taken up in 5% MeOH-dcm (400 mL) and the organic phase was washed with dilute brine (40 mL), dried over sodium sulfate concentrated to afford crude (S)—N-(2-bromo-9-(hydroxymethyl)-7-iodo-9H-xanthen-9-yl)-2-chloroacetamide, which was used in the next step without further purification.

1. temperatureto warm naturally to RT
2. concentrationthe reaction was concentrated
3. extractionthe aqueous phase was extracted with 7.5% MeOH-DCM (3×133 mL)
4. washwashed with aqueous 1 M Na2CO3 (30 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in THF (100 mL)
8. additionaqueous 1 M Na2CO3 (15 mL) was added
9. concentrationThe reaction was concentrated
10. washthe organic phase was washed with dilute brine (40 mL)
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated

ORD record

ord-43f47c70679b48c297e62e793e01757a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497264B2