Triethylamine → 6-Cyclopentyl-4-hydroxy-6-[4-(3-hydroxy-phenyl)-but-3-ynyl]-3-(thiazol-2-ylsulfanyl)-5,6-dihydro-pyran-2-one

Temperature

50 °C

To a solution of 3-chloro-6-cyclopentyl-6-[4-(3-hydroxy-phenyl)-but-3-ynyl]-dihydro-pyran-2,4-dione (216 mg, 0.6 mmol) from Step 5 below and 2-mercaptothiazole (141 mg, 1.2 mmol) in DMF (6 mL) was added triethylamine (0.15 mL, 1.2 mmol). The reaction was stirred at 50° C. for 2.5 hours and then quenched with 10 mL of saturated ammonium chloride. The mixture was further acidified to a pH of 1-2 with 1 N HCl. To this mixture was added 10 mL CH2Cl2 and the layers were separated. The aqueous was extracted with 2×10 mL CH2Cl2, and the organic layers were combined. After drying the organic layer over MgSO4, the solids were filtered away and the liquid was concentrated to an oil. The oil was chromatographed on silica to yield the desired product (28 mg, 11% yield). 1H NMR (CDCl3) δ: 1.09-1.58 (m, 8H), 1.93-2.05 (m, 3H), 2.58-2.82 (m, 4H), 6.59 (d, J=6.82 Hz, 2H), 6.65 (d, J=7.58 Hz, 1H), 6.96-7.00 (m, 1H), 7.32 (d, J=3.28 Hz, 1H), 7.46 (d, J=3.28 Hz, 1H). MS (ESI): 440 (M−H).

1. customquenched with 10 mL of saturated ammonium chloride
2. additionTo this mixture was added 10 mL CH2Cl2
3. customthe layers were separated
4. extractionThe aqueous was extracted with 2×10 mL CH2Cl2
5. dry with materialAfter drying the organic layer over MgSO4
6. filtrationthe solids were filtered away
7. concentrationthe liquid was concentrated to an oil
8. customThe oil was chromatographed on silica

ORD record

ord-5754c755ee4f44b0b6768a3900eaacd0

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07473790B2