Sodium borohydride → HCID 86652901, compound

Temperature

-10 °C

To a two-neck flask with a nitrogen inlet, compound 9 (5.2 g, 18 mmol, 1 equiv) was dissolved in 200 mL methanol/THF (10/1). The solution was cooled to −10° C. in a salted ice bath, followed by the addition of sodium borohydride (0.8 g, 21 mmol, 1.2 equiv). The mixture was stirred at 0° C. for 20 min, then allowed to warm to rt and stirred for an additional 20 min. The mixture was concentrated under vacuum, cooled to 0° C. and acidified with diluted HCl solution. The aqueous solution was extracted with ethyl acetate. The combined organic extracts were washed with brine (200 mL) and dried over MgSO4. After filtration the solvent was removed under vacuum to afford crude product as a yellowish solid. This was chromatographed on a silica gel column (eluent: 0% to 5% of methanol in CH2Cl2) to give 10 as a white solid (4.95 g, yield: 95%). 1H NMR δ=7.10 (d, J=1.8, 1H), 6.97 (dd, J1=1.8, J2=8, 1H), 6.93 (d, J=8, 1H), 4.78 (d, J=2.3, 2H, —OCH2C≡CH), 4.64 (d, J=5.8, 2H, —CH2OH), 4.34 (t, J=6.6, 2H, —OCH2CH2Br), 3.66 (t, J=6.6, 2H, —OCH2CH2Br), 2.51 (t, J=2.3, 1H, —C≡CH), 1.68 (t, J=5.8, 1H, —CH2OH). 13C NMR δ=147.90, 145.60, 135.34, 121.32, 115.46, 114.92, 78.78 (—C≡CH), 76.12 (—C≡CH), 70.54 (—CH2OH), 66.28 (—OCH2CH2Br), 57.38 (—OCH2C≡CH), 29.32 (—OCH2CH2Br). HRMS calculated for C12H11BrO3 (M+Na+), 354.9807; found, 354.9810.

1. temperatureto warm to rt
2. stirringstirred for an additional 20 min
3. concentrationThe mixture was concentrated under vacuum
4. temperaturecooled to 0° C.
5. extractionThe aqueous solution was extracted with ethyl acetate
6. washThe combined organic extracts were washed with brine (200 mL)
7. dry with materialdried over MgSO4
8. filtrationAfter filtration the solvent
9. customwas removed under vacuum
10. customto afford crude product as a yellowish solid
11. customThis was chromatographed on a silica gel column (eluent: 0% to 5% of methanol in CH2Cl2)

ORD record

ord-9a8e102d359d49eab988e0f0b0a87af6

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08470587B2