Diisopropylethylamine → [(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester

HRID 582412Notes

Reaction equation

NCC1C=C(C=CC=1)[C:6]([NH:8][C@@H:9]([C:21](=[O:36])[N:22]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:33][CH2:34][OH:35])[CH3:23])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)=[O:7].[OH:40]N1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CNC[CH2:65][C:66]1[CH:75]=CC=C[C:67]=1OCCO.C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:66]([O:7][C:6](=[O:40])[NH:8][C@@H:9]([C:21](=[O:36])[N:22]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:33][CH2:34][OH:35])[CH3:23])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)([CH3:75])([CH3:67])[CH3:65]

Participants

Conditions

Temperature: 0 °C

Procedure

3-Aminomethyl-N-[(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]benzamide ##STR154## [(1R)-1-(N-{2-[2-(2-Hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester ##STR155## (2R)-2-(tert-Butoxycarbonylamino)-3-(2-naphthyl)propionic acid (654 mg, 2.07 mmol) was dissolved in N,N-dimethylformamide (4 ml) and dichloromethane (4 ml). 1-Hydroxy-7-azabenzotriazole (282 mg, 2.07 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (397 mg, 2.07 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of 2-(2-(2-(methylamino)ethyl)phenoxy)ethanol (434 mg, 2.07 mmol) in dichloromethane (4 ml) and ethyldiisopropylamine (0.36 ml, 2.07 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml). The aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (70 g), using ethyl acetate/heptane 1:1 as eluent, to give 539 mg of [(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester.

Workup

stirringThe reaction mixture was stirred for 16 h, while it
temperaturewas warming up to room temperature
washwashed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml)
extractionThe aqueous phase was extracted with ethyl acetate (2×20 ml)
washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml)
dry with materialdried over magnesium sulfate
customThe solvent was removed in vacuo
customThe crude product was purified by flash chromatography on silica (70 g)

Sources & evidence

ORD record: ord-69d787261ac14059a5402ef9e3ca7eab
Source dataset: uspto-grants-1999_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05922770

Reaction notes

Loading…