4-Methylmorpholine → 2-Oxo-(3S)-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1,5-benzodiazepine

HRID 2230463Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][NH:14][C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[C:16]=1[NH2:23])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.CCOC(C)=O>C1COCC1>[O:11]=[C:10]1[NH:23][C:16]2[C:17]([CH3:22])=[CH:18][C:19]([CH3:21])=[CH:20][C:15]=2[NH:14][CH2:13][C@@H:9]1[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

Conditions

Temperature: 0 °C

Procedure

A 0° C. solution of (2S)-2-tert-butoxycarbonylamino-3-(2-amino-3,5-dimethylphenyl-amino)-propionic acid (763 mg, 2.36 mmol) and N-methylmorpholine (483 mg, 4.78 mmol) in 60 ml of anhydrous THF was treated dropwise with isobutylchloroformate (352 mg, 2.5 mmol). The reaction was stirred for 2 h at 0° C., at RT for 1 h and poured over EtOAc. The mixture was washed with aq. 5% NaHSO4, sat. aq. NaHCO3, and sat. aq. NaCl, dried over NaSO4, and concentrated in vacuo. Chromatography (flash, SiO2, 10% to 25% to 50% EtOAc/CH2Cl2) gave 490 mg (68%) of the desired product.

Workup

washThe mixture was washed with aq. 5% NaHSO4, sat. aq. NaHCO3, and sat. aq. NaCl
dry with materialdried over NaSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-ab6fbbec71f54587970e861435abf7a6
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06423840B1

Reaction notes

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