Dicyclohexylcarbodiimide → HCID 57114915、化合物

To a stirred solution of 1,2-bis(4-fluorophenyl)-2-propylamine (11.07 g, 0.045 mol) in 200 ml of chloroform under nitrogen, were added N-CBZ-L-alanine (10.0 g, 0.045 mol) and then a solution of dicyclohexylcarbodiimide (9.90 g, 0.05 mol) in 100 ml of chloroform, and the mixture was stirred for 16 hours. The precipitated solid was removed by filtration and the solvent evaporated. The residue was treated with ethyl acetate (100 ml), filtered, an additional 300 ml of ethyl acetate added, and then washed with 1% cold HCl (100 ml), brine (2×100 ml), dried over MgSO4, and the solvent evaporated. The residue was dissolved in 450 ml of methanol and 35 ml of 10% HCl and hydrogenated at 40 psi in a Parr apparatus over 3.0 g of 5% Pd/C catalyst for 3 hours. The catalyst was removed by filtration, the solvent evaporated and the residue dissolved in water (200 ml) and chloroform (300 ml), basified to pH 11 with 50% NaOH, shaken and separated. The aqueous phase was extracted with chloroform (2×200 ml), and the combined organic phases were washed with water (2×200 ml), and dried over MgSO4. Removal of solvent gave a white solid. This solid was recrystallized from cyclohexane/hexane and then from hexane/ethanol, and vacuum dried to give 1.5 g of (2S)-2-amino-N-[1,2-bis(4-fluorophenyl)-1-methylethyl]propanamide, mp. 134°-135° C.

1. customThe precipitated solid was removed by filtration
2. customthe solvent evaporated
3. additionThe residue was treated with ethyl acetate (100 ml)
4. filtrationfiltered
5. additionan additional 300 ml of ethyl acetate added
6. washwashed with 1% cold HCl (100 ml), brine (2×100 ml)
7. dry with materialdried over MgSO4
8. customthe solvent evaporated
9. dissolutionThe residue was dissolved in 450 ml of methanol
10. customThe catalyst was removed by filtration
11. customthe solvent evaporated
12. dissolutionthe residue dissolved in water (200 ml)
13. customseparated
14. extractionThe aqueous phase was extracted with chloroform (2×200 ml)
15. washthe combined organic phases were washed with water (2×200 ml)
16. dry with materialdried over MgSO4
17. customRemoval of solvent
18. customgave a white solid
19. customThis solid was recrystallized from cyclohexane/hexane
20. dry with materialfrom hexane/ethanol, and vacuum dried

ORDレコード

ord-1eb34a79aa124905a4a5ea43ec76b5dc

出典データセット

uspto-grants-1995_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05382683