Water → 3-nitro-4-pyrrolidin-1-ylbenzoic acid

HRID 336231Notes

Reaction equation

F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.[OH-].[Li+].O>CN(C=O)C.C1COCC1>[N+:13]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=1[N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C:6]([OH:8])=[O:7])([O-:15])=[O:14]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Chontech 01072; 500 mg; 2.35 mmol; 1 eq.) and pyrrolidine (Fluka 83240; 500.48 mg; 7.04 mmol; 3 eq.) in DMF (2 mL) was stirred at 60° C. for 4 hours. The reaction mixture was then partitioned between ethyl acetate and aq. NH4Cl. The organic layer was washed three times with aq. NH4Cl then brine, dried over magnesium sulfate and concentrated in vacuo to give a yellow oil. The latter was taken up in THF (5 mL) and lithium hydroxide (280.86 mg; 11.73 mmol; 5 eq.) then water (5 mL) were added. The reaction mixture was stirred at room temperature for 16 hours then the THF was evaporated and the residue was diluted with water. After acidification with AcOH, the formed precipitate was filtered and dried under high vacuum to afford the title compound (497 mg, 90%) as a yellow solid.

Workup

customThe reaction mixture was then partitioned between ethyl acetate and aq. NH4Cl
washThe organic layer was washed three times with aq. NH4Cl
dry with materialbrine, dried over magnesium sulfate
concentrationconcentrated in vacuo
customto give a yellow oil
stirringThe reaction mixture was stirred at room temperature for 16 hours
customthe THF was evaporated
additionthe residue was diluted with water
filtrationAfter acidification with AcOH, the formed precipitate was filtered
customdried under high vacuum

Sources & evidence

ORD record: ord-6e23f178f2c341a1bbfaf8a42dafbc49
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889668B2

Reaction notes

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