Acetonitrile → HCID 86592505, compound

A solution of lithium hexamethyldisilazide in THF (1M, 0.29 ml, 0.29 mmol) was added at 0–5° C. to a solution of allyl (2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(2-mercapto-1,3-thiazol-4-yl)-3,6-dihydro-1(2 H)-pyridinecarboxylate (122 mg, 0.29 mmol) in THF (4.3 ml) and the mixture was stirred for 10 minutes. To the reaction solution was added at 0° C. a solution of allyl (4R,5R,6S)-3-[(diphenoxyphosphino)oxy-4-methyl-7-oxo-6-{(1R)-1-[(trimethylsilyl)oxy]ethyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in acetonitrile (30%, 1.09 g, 0.58 mmol) and the solution was allowed to stand in a refrigerator for 19 hours. To the reaction solution was added ice water and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was dissolved in THF (5.65 ml). To the solution were added at 0–5° C. acetic acid (215 μl) and tetrabutylammonium fluoride in THF (1M, 1.5 ml, 1.5 mmol). After reaction for 20 hours, to the reaction mixture was added ice water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/3→10% methanol in chloroform) to give allyl (4R,5S,6S)-3-({4-[(2R)-1-[(allyloxy)carbonyl]-2-(hydroxymethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1,3-thiazol-2-yl}sulfanyl)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (110 mg, 68%). IR (KBr) 3426, 2933, 1772, 1700, 1559, 1457, 1136 cm−1 1H NMR (300 MHz, CDCl3) δ 1.10 (3 H, d, J=7.3 Hz), 1.31 (3 H, d, J=6.2 Hz), 2.50 (1 H, d, J=17.4 Hz), 2.62–2.73 (1 H, m), 3.25 (1 H, d, J=2.8, 7.0 Hz), 3.45–3.96 (4 H, m), 4.17–4.27 (2 H, m), 4.41–4.86 (6 H, m), 5.19–5.47 (4 H, m), 5.87–6.03 (2 H, m), 6.63 (1 H, s), 7.11 (1 H, s).

1. waitto stand in a refrigerator for 19 hours
2. extractionthe reaction mixture was extracted with ethyl acetate
3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
4. dry with materialdried over anhydrous sodium sulfate
5. customAfter removal of the solvent in vacuo
6. dissolutionthe residue was dissolved in THF (5.65 ml)
7. customAfter reaction for 20 hours
8. extractionthe mixture was extracted with ethyl acetate
9. washThe organic layer was washed with a saturated aqueous sodium chloride solution
10. dry with materialdried over anhydrous sodium sulfate
11. customAfter removal of the solvent in vacuo
12. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/3→10% methanol in chloroform)

ORD record

ord-789102361b2a419180a6f6f02aa1a518

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07163936B2