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

HRID 926355Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:15](=[O:20])C(Cl)(Cl)Cl)[N:9]2[CH2:14][CH2:13][O:12][CH2:11][C:10]=12)=[O:5])[CH3:2].[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:15]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[N:9]2[CH2:14][CH2:13][O:12][CH2:11][C:10]=12)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 6-(2,2,2-trichloro-acetyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester (Comp. No. 4a) (1.2 g, 3.52 mmol) in anhydrous tetrahydrofuran (7 ml) was added pyrrolidine (0.376 g, 5.28 mmol). The resulting mixture was stirred at 55° C. for 1.5 h, and then evaporated to dryness. To the residue was added 15 ml water and 30 ml ethyl acetate and the layers were separated. The aqueous layer was extracted once with 15 ml ethyl acetate. The organic layers were combined and evaporated to dryness. The product was purified by flash chromatography to give 0.95 g (92%) of 6-(pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester. LC/MS (method 4): Rt=1.14 min; m/z=293.22 (M+H+).

Workup

customevaporated to dryness
additionTo the residue was added 15 ml water and 30 ml ethyl acetate
customthe layers were separated
extractionThe aqueous layer was extracted once with 15 ml ethyl acetate
customevaporated to dryness
customThe product was purified by flash chromatography

Sources & evidence

ORD record: ord-fb4e02c1f9a84a66b4791456c4ec89de
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284333B2

Reaction notes

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