Water → (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-oxo-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 417654Notes

Reaction equation

HRID 417654 reaction equation
[CH3:1][O:2][C:3](=[O:32])[NH:4][CH:5]([C:9]([N:11]1[CH:19]([C:20]2[NH:21][C:22]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][CH:26]=3)=[CH:23][N:24]=2)[CH2:18][C:13]2(OCC[O:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].O.CC1C=CC(S(O)(=O)=O)=CC=1.O>CC(C)=O>[CH3:1][O:2][C:3](=[O:32])[NH:4][CH:5]([C:9]([N:11]1[CH2:12][C:13](=[O:14])[CH2:18][CH:19]1[C:20]1[NH:21][C:22]([C:25]2[CH:26]=[CH:27][C:28]([Br:31])=[CH:29][CH:30]=2)=[CH:23][N:24]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 962WaterHCID 521998p-Toluenesulfonic acid monohydrate2×HCID 66621245(1-{8-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 66620390(1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-oxo-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 44.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

(1-{8-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (230.0 mg, 0.453 mmol) was dissolved in acetone (10 mL) and water (0.2 mL) and p-TsOH.H2O (53 mg, 0.278 mmol) were added. The reaction was heated at 60° C. for 20 hours, after which additional p-TsOH.H2O (53 mg, 0.278 mmol) was added heating at 60° C. was continued. After three days, all volatiles were removed in vacuo. The crude material was taken into EtOAc and was washed with aqueous sodium bicarbonate solution and dried over sodium sulfate. Filtration and evaporation of solvents in vacuo gives the crude product. The crude material was purified via silica gel chromatography (eluent: EtOAc containing 10% MeOH/hexanes) to yield the product (93.9 mg, 0.202 mmol). LCMS-ESI+: calc'd for C20H23BrN4O4: 463.3 (M+). Found: 463.6 (M+H+).

Workup

  1. temperatureheating at 60° C.
  2. customall volatiles were removed in vacuo
  3. washwas washed with aqueous sodium bicarbonate solution
  4. dry with materialdried over sodium sulfate
  5. filtrationFiltration and evaporation of solvents in vacuo
  6. customgives the crude product
  7. customThe crude material was purified via silica gel chromatography (eluent: EtOAc containing 10% MeOH/hexanes)

Sources & evidence

ORD record
ord-55fb4b2c941d4a3a9c50368736f20732
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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