Cesium carbonate → (1R,3S)-methyl 1-amino-3-(4-(7-methoxyhept-1-ynyl)phenyl)cyclopentanecarboxylate

Temperature

90 °C

To a 50 mL round bottomed flask equipped with a reflux condenser was charged successively (1R,3S)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate hydrochloride salt (0.500 g, 1.494 mmol), trans-bis(benzonitrile)dichloropalladium(II) (0.029 g, 0.075 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.107 g, 0.224 mmol), and cesium carbonate (1.947 g, 5.98 mmol). The flask was evacuated and back-filled with nitrogen for three cycles. Then 7-methoxyhept-1-yne (1.16 g, 9.19 mmol) as a solution in acetonitrile (7.0 ml) was added via syringe. The reaction mixture was heated to about 90° C. After about 4 hours the reaction mixture was cooled to ambient temperature and partitioned into water (50 mL) and ethyl acetate (50 mL). The organic phase was separated, washed with saturated sodium bicarbonate solution (50 mL), brine (50 mL), then dried (MgSO4) and concentrated to yield 1.98 g of crude yellow oil. The crude material was purified via Analogix flash chromatography system using RediSep RS 12 g column, with a gradient of 0-5% methanol in ethyl acetate over 25 min. at 15 mL/min. Fractions containing product were combined and concentrated to yield 0.5 g of greenish yellow oil of (1R,3S)-methyl 1-amino-3-(4-(7-methoxyhept-1-ynyl)phenyl)cyclopentanecarboxylate which was used in the next step without further purification.

1. customTo a 50 mL round bottomed flask equipped with a reflux condenser
2. customThe flask was evacuated
3. additionback-filled with nitrogen for three cycles
4. temperatureAfter about 4 hours the reaction mixture was cooled to ambient temperature
5. custompartitioned into water (50 mL) and ethyl acetate (50 mL)
6. customThe organic phase was separated
7. washwashed with saturated sodium bicarbonate solution (50 mL), brine (50 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customto yield 1.98 g of crude yellow oil
11. customThe crude material was purified via Analogix flash chromatography system
12. additionFractions containing product
13. concentrationconcentrated

ORD record

ord-5cf1e57ba16441059002620f96534e61

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217027B2