Triethylamine → (S)-3-(1-carbamoyl-1,1-diphenylmethyl)-1-(7-hydroxyhept-1-yl)pyrrolidine

Temperatur

50 °C

To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (40 g, 142.7 mmol) and triethylamine (59.6 mL, 428 mmol) in acetonitrile (1.1 L) at 40° C. under a nitrogen atmosphere was added 7-bromo-1-heptanol (24 mL, 146 mmol) in acetonitrile (100 mL) dropwise. The reaction mixture was heated to 50° C. for 9 hours. The reaction mixture was allowed to cool before removing the solvent under reduced pressure. The crude residue was dissolved in dichloromethane (500 mL) and the organic layer washed with saturated aqueous sodium bicarbonate (2×300 mL), followed by water (300 mL) and saturated aqueous sodium chloride (300 mL), and then dried over magnesium sulfate (10 g). The magnesium sulfate was filtered off and washed with dichloromethane (100 mL). The solvent was then removed in vacuo to give the crude product which was purified on a short column (SiO2) by varying the eluant from 19:1:0.1 to 3:1:0.1 CH2Cl2/MeOH/NH4OH to give 31.35 g of the title intermediate as a white solid (56% yield; >95% purity by HPLC Method A).

1. temperatureto cool
2. custombefore removing the solvent under reduced pressure
3. dissolutionThe crude residue was dissolved in dichloromethane (500 mL)
4. washthe organic layer washed with saturated aqueous sodium bicarbonate (2×300 mL)
5. dry with materialdried over magnesium sulfate (10 g)
6. filtrationThe magnesium sulfate was filtered off
7. washwashed with dichloromethane (100 mL)
8. customThe solvent was then removed in vacuo
9. customto give the crude product which
10. customwas purified on a short column (SiO2)

ORD-Eintrag

ord-111069edddb340e6bda1e66ffe6db2d9

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08080565B2