Pyrrolidine → Methyl 3-bromo-5-(pyrrolidine-1-carbonyl)benzoate

HRID 1845178Notes

Reaction equation

HRID 1845178 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[C:5]([OH:7])=O.Cl.CN(C)[CH2:18][CH2:19][CH2:20][N:21]=[C:22]=NCC.O.ON1C2C=CC=CC=2N=N1.N1CCCC1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]([CH:8]=[C:4]([C:5]([N:21]2[CH2:22][CH2:18][CH2:19][CH2:20]2)=[O:7])[CH:3]=1)[C:11]([O:13][CH3:14])=[O:12]

Participants

7

Reactant 5

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 225936413-Bromo-5-(methoxycarbonyl)benzoic acid

Product 1

HCID 58188186Methyl 3-bromo-5-(pyrrolidine-1-carbonyl)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 5.6 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.1 g, 11 mmol), 1-hydroxybenzotriazole hydrate (1.7 g, 11 mmol), methylene chloride (20 mL) were added pyrrolidine (0.58 g, 8.2 mmol) and N,N-diisopropylethylamine (1.9 mL, 11 mmol). The mixture was stirred at room temperature overnight, and then diluted with methylene chloride (200 mL). The organic phase was washed with aq. BaHCO3, and aq. K2HPO4, brine, dried over Na2SO4, and concentrated. The residue was purified via flash chromatography (silica gel column, 0-100 EtOAc/hexane) to afford the desired product as a clear oil. 1H NMR (400 MHz, DMSO-d6): 8.12 (t, J=1.8 Hz, 1H), 7.80-7.98 (m, 2H), 3.88 (s, 3H), 3.47 (t, J=6.7 Hz, 2H), 3.36 (t, J=6.5 Hz, 2H), 1.89-1.80 (m, 4H).

Workup

  1. washThe organic phase was washed with aq. BaHCO3, and aq. K2HPO4, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified via flash chromatography (silica gel column, 0-100 EtOAc/hexane)

Sources & evidence

ORD record
ord-7f86ac23ef654f9dbaea975a5624318e
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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