Sodium Iodide → (+)-(5R)-5-Ethyl-5-hydroxy-2,5,6,9-tetrahydro-8-oxa-2-aza-benzocycloheptene-1,7-dione

Temperature

60 °C

To a dry round-bottom flask was added lactone 10b (0.07 g, 0.3 mmol) followed by dry acetonitrile (1 mL). Sodium iodide (0.07 g, 0.49 mmol) was added followed by chlorotrimethylsilane (0.06 mL, 0.49 mmol). The resulting mixture was stirred at rt for 15 min at which point H2O was added (2.7 μL, 0.15 mmol) and the reaction mixture was heated to 60° C. for 7 h. The mixture was then poured into a 1:1 solution of 5% sodium sulfite/brine (7 mL) and then quickly extracted with ethyl acetate (4×5 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was subjected to flash chromatography (MeOH/CH2Cl2 5:95) to afford pure 11 as pale yellow oil (10.4 mg, 16%). IR (MeOH, NaCl,cm−1) 3370(br), 1655, 1049, 1025, 823, 768; 1H NMR (300 MHz, CD3OD) δ0.91 (t, J=7.5 Hz, 3H), 1.82 (m, 2H), 3.10 (d, J=13.8 Hz, 1H), 3.40 (d, J=13.8 Hz, 1H), 5.30 (d, J=15.2 Hz, 1H), 5.46 (d, J=15.2 Hz, 1H), 6.57 (d, J=7 Hz, 1H), 7.35 (d, J=7 Hz, 1H); 13C NMR (75 MHz, CDCl3/CD3OD) δ6.76, 35.22, 41.46, 60.98, 72.43, 105.93, 122.42, 132.76, 156.35, 161.60, 172.57; HRMS (EI) m/z calcd for C11H13NO4 (M+) 223.0845, found 223.0851; LRMS (EI) m/z 224(M+H, 32), 195(21), 163(43), 153(100), 91(40), 77(19), 55(24); [α]D23=+35.0 (c=0.08, MeOH).

1. additionwas added (2.7 μL, 0.15 mmol)
2. extractionquickly extracted with ethyl acetate (4×5 mL)
3. dry with materialThe organic layer was dried over MgSO4
4. concentrationconcentrated under reduced pressure

ORD record

ord-f01e2071c1ec42e88458cb7570dcb45b

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06723853B2