2-Bromopropanedial → HCID 86700106, compound

To a solution of material from Example 48 (5.25 g, 15.75 mmol) in a mixture of THF (178 mL) and acetic acid (29.6 mL), is added sequentially sodium acetate (1.55 g, 18.91 mmol) and 2-bromomalonaldehyde (2.75 g, 17.33 mmol) and the reaction is stirred at room temp. for 2 h. The solvent is removed in vacuo and the residue is partitioned between water (25 mL) and CH2Cl2 (40 mL). The aqueous phase is extracted with CH2Cl2 (2×20 mL), neutralized to pH 8 with solid sodium bicarbonate and extracted again with CH2Cl2 (3×25 mL). The organic layers are combined, washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue is purified by BIOTAGE® Silica gel chromatography on a 160 g Thompson Single Step silica cartridge using a linear gradient from 60% Hexanes/Ethyl Acetate to 50% Hexanes/Ethyl Acetate over 5 column volumes to give 3.8 g (62.6%) of the title compound as a yellow foam. LC/MS (Condition A): ret. T=3.52 min, (M+Na) 408.15. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.64 (1 H, s), 8.94 (1 H, br. s.), 8.06 (1 H, s), 7.28 (1 H, d, J=7.78 Hz), 3.79-3.96 (1 H, m), 1.92-2.05 (1 H, m), 1.75-1.92 (1 H, m), 1.43 (3 H, br. s.), 1.40 (18 H, d, J=1.76 Hz).

1. customThe solvent is removed in vacuo
2. customthe residue is partitioned between water (25 mL) and CH2Cl2 (40 mL)
3. extractionThe aqueous phase is extracted with CH2Cl2 (2×20 mL)
4. extractionextracted again with CH2Cl2 (3×25 mL)
5. washwashed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated to dryness
9. customThe residue is purified by BIOTAGE® Silica gel chromatography on a 160 g Thompson Single Step silica cartridge

ORD record

ord-53a2e6d399ef44fdbd1702eabf0e05b3

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169295B2