1-Hydroxybenzotriazole → 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester

HRID 926359Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:15]([OH:17])=O)[N:9]2[CH2:14][CH2:13][O:12][CH2:11][C:10]=12)=[O:5])[CH3:2].ON1[C:23]2[CH:24]=[CH:25][CH:26]=C[C:22]=2[N:21]=N1.Cl.C(N=C=NCCCN(C)C)C.C[C@H]1CCCN1>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:15]([N:21]2[CH2:22][CH2:23][CH2:24][C@@H:25]2[CH3:26])=[O:17])[N:9]2[CH2:14][CH2:13][O:12][CH2:11][C:10]=12)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6,8-dicarboxylic acid 8-ethyl ester (Comp. No. 5a) (6.09 g, 25.5 mmol) in dimethylformamide (60 ml) was added 1-hydroxybenzotriazole (3.785 g, 0.028 mol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.37 g, 28 mmol). The mixture was stirred for 1 h at 50° C., then (S)-2-methylpyrrolidine (2.385 g, 28 mmol) was added and the mixture was stirred at 25° C. overnight. Solvents were evaporated, the residue was dissolved in dichloromethane and washed against saturated aqueous sodium hydrogencarbonate to give 7.8 g (100%) of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester. LC/MS (method 2): Rt=1.06 min; m/z=307.19 (M+H+).

Workup

stirringthe mixture was stirred at 25° C. overnight
customSolvents were evaporated
dissolutionthe residue was dissolved in dichloromethane
washwashed against saturated aqueous sodium hydrogencarbonate

Sources & evidence

ORD record: ord-fd0ac5c935324a4c9cc455117ce828f3
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284333B2

Reaction notes

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