Ethylmorpholine → 2'-isobutyl-4-methyl-2'-(N-methyl-N-tert.-butoxycarbonyl-L-alanyl)valerohydrazide

HRID 1979207Notes

Reaction equation

[CH3:1][N:2]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:3]([C:5]([OH:7])=O)[CH3:4].C(N1CCOCC1)C.ClC(OCC(C)C)=O.O1CCCCC1ONC([C@H]([C@@H:51]([CH2:60][CH:61]([CH3:63])[CH3:62])[C:52]([NH:54][NH:55][CH2:56][CH:57]([CH3:59])[CH3:58])=[O:53])C/C=C/C1C=CC=CC=1)=O>O1CCCC1.C(OCC)(=O)C>[CH2:56]([N:55]([C:5](=[O:7])[C@H:3]([CH3:4])[N:2]([CH3:1])[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[NH:54][C:52](=[O:53])[CH2:51][CH2:60][CH:61]([CH3:63])[CH3:62])[CH:57]([CH3:59])[CH3:58]

Participants

Conditions

Temperature: -10 °C

Procedure

A solution of 0.233 g of N-methyl-N-tert.-butoxycarbonyl-L-alanine in 10 ml of tetrahydrofuran was cooled to −10° C. and treated with 0.140 ml of N-ethylmorpholine and 0.143 ml of isobutyl chloroformate. The mixture was stirred for a further 10 minutes at −10° C. and then treated with 0.459 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)-carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methylvalerohydrazide. The mixture was allowed to warm to 0° C. and stirring was continued for 45 minutes. The mixture was then diluted with ethyl acetate and washed in sequence with 5% aqueous citric acid, 5% aqueous sodium hydrogen carbonate and brine. Drying over magnesium sulphate and evaporation gave 0.608 g of (E)-2(R)-[1(S)-(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methyl-2′-(N-methyl-N-tert.-butoxycarbonyl-L-alanyl)valerohydrazide in the form of a white solid.

Workup

temperatureto warm to 0° C.
stirringstirring
waitwas continued for 45 minutes
washwashed in sequence with 5% aqueous citric acid, 5% aqueous sodium hydrogen carbonate and brine
dry with materialDrying over magnesium sulphate and evaporation

Sources & evidence

ORD record: ord-8fb7a26a98ee49a5a641f5a58d17b0eb
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06239151B1

Reaction notes

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