Triethylamine → HCID 11786472, compound

Sulfur trioxide pyridine complex (3.02 g, 19.1 mmol) was added to a stirred solution of alcohol 13 (3.26 g, 6.31 mmol) and triethylamine (2.6 mL, 19.1 mmol) in anhydrous CH2Cl2 (6 mL) and DMSO (12 mL) at 0° C. The reaction mixture was stirred at the ambient temperature for 1 h. The mixture was diluted with Et2O (100 mL) and washed with aqueous 0.5 N HCl (50 mL) and brine (10 mL). The separated organic layer was dried over MgSO4. Filtration and concentration followed by short flash column chromatography (hexane/EtOAc 4:1) provided the crude aldehyde as a colorless oil, which was used without further purification. A solution of the aldehyde in THF (25 mL) and H2O (12 mL) was treated with 2-methyl-2-butene in THF (2M, 18 mL, 9.0 mmol), NaH2PO4.H2O (2.6 g, 18.8 mmol) and NaClO2 (2.1 g, 18.6 mmol). The reaction mixture was stirred for 2 h, diluted with 1N HCl (20 mL) and extracted with CH2Cl2 (2×40 mL). The combined organic layers were dried over MgSO4, concentrated in vacuo and the crude acid was used for the next reaction without further purification. N,O-Dimethylhydroxylamine hydrochloride (0.62 g, 6.36 mmol), Et3N (0.88 mL, 6.31 mmol), DMAP (0.63 mmol) were successively added to a solution of the crude acid in CH2Cl2 (10 mL). The reaction mixture was cooled to 0° C. and DCC (1.30 g, 6.30 mmol) was added. The mixture was stirred at ambient temperature for 15 h and filtered. The filtrate was washed with 0.5 N HCl, saturated aqueous NaHCO3, and brine, dried over anhydrous MgSO4 and concentrated. Purification by column chromatography over silica gel (hexane/EtOAc 4:1) gave the Weinreb amide 15 (2.65 g, 73% for 3 steps) as a colorless oil: IR (CHCl3) 2956, 2929, 2855, 1663, 1448, 1252, 1083, 1032, 836 cm−1; 1H NMR (300 MHz, CDCl3) ε7.58 m, 6H), 7.37 (m, 9H), 5.89 (dd, J=15.6, 7.6 Hz, 1H), 5.72 (dt, J=15.6, 5.2 Hz, 1H), 4.38 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 3.74 (s, 3H), 3.70 (d, J=5.1 Hz, 2H), 3.27 (s, 3H), 2.79 (dd, J=15.1, 7.4 Hz, 1H), 2.52 (m, 2H), 1.20 (d, J=6.9 Hz, 3H), 1.02 (s, 9H), 0.22 (s, 3H), 0.16 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 172.6, 144.2, 133.3, 128.5, 127.7, 127.5, 126.8, 86.7, 72.4, 64.8, 61.2, 42.4, 36.3, 31.9, 25.8, 18.0, 15.7, −4.6, −5.0; LRMS (ESI) 596.2 [M+Na]+, 449.2, 243.0; HRMS (ESI) calcd for C35H47O4NSiNa 596.3172 [M+Na]+, found 596.3165; [α]20D−14.7 (c 0.65 , CHCl3).

1. washwashed with aqueous 0.5 N HCl (50 mL) and brine (10 mL)
2. dry with materialThe separated organic layer was dried over MgSO4
3. filtrationFiltration and concentration
4. customprovided the crude aldehyde as a colorless oil, which
5. customwas used without further purification
6. stirringThe reaction mixture was stirred for 2 h
7. extractionextracted with CH2Cl2 (2×40 mL)
8. dry with materialThe combined organic layers were dried over MgSO4
9. concentrationconcentrated in vacuo
10. customthe crude acid was used for the next reaction without further purification
11. temperatureThe reaction mixture was cooled to 0° C.
12. stirringThe mixture was stirred at ambient temperature for 15 h
13. filtrationfiltered
14. washThe filtrate was washed with 0.5 N HCl, saturated aqueous NaHCO3, and brine
15. dry with materialdried over anhydrous MgSO4
16. concentrationconcentrated
17. customPurification by column chromatography over silica gel (hexane/EtOAc 4:1)

ORD record

ord-8ebce85d63c24a3db88c4d00f0fdb495

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07321046B2