4-Nitrophenyl quinuclidin-3-yl carbonate → Quinuclidin-3-yl (1-(5-bromothiophen-3-yl)cyclopropyl)carbamate

HRID 2274898Notes

Reaction equation

HRID 2274898 reaction equation
[Br:1][C:2]1[S:6][CH:5]=[C:4]([C:7]([NH2:10])([CH3:9])[CH3:8])[CH:3]=1.[C:11](=O)([O:22][CH:23]1[CH:28]2[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]2)[CH2:24]1)[O:12]C1C=CC([N+]([O-])=O)=CC=1>C1COCC1.CN(C)C1C=CN=CC=1>[N:25]12[CH2:30][CH2:29][CH:28]([CH2:27][CH2:26]1)[CH:23]([O:22][C:11](=[O:12])[NH:10][C:7]1([C:4]3[CH:3]=[C:2]([Br:1])[S:6][CH:5]=3)[CH2:9][CH2:8]1)[CH2:24]2

Participants

5

Reactant 2

HCID 585817304-Nitrophenyl quinuclidin-3-yl carbonateHCID 683279972-(5-Bromothiophen-3-yl)propan-2-amine

Product 1

HCID 131733415Quinuclidin-3-yl (1-(5-bromothiophen-3-yl)cyclopropyl)carbamateYield 49.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(5-bromothiophen-3-yl)propan-2-amine (0.366 g, 1.66 mmol) in THF (10 mL) was added 4-nitrophenyl quinuclidin-3-yl carbonate (0.571 g, 1.95 mmol) and a few granules of 4-(dimethylamino)pyridine. The mixture was refluxed overnight, concentrated and partitioned between ethyl acetate (50 mL) and aqueous NaHCO3 (50 mL). The organic layer was washed again with aqueous NaHCO3 (1×50 mL), dried (Na2SO4) and concentrated. The resulting dirty yellow gum was purified by flash chromatography using a chloloform/methanol/ammonia gradient to afford quinuclidin-3-yl(1-(5-bromothiophen-3-yl)cyclopropyl)carbamate as an off-white solid (0.305 g, 49%).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. concentrationconcentrated
  3. custompartitioned between ethyl acetate (50 mL) and aqueous NaHCO3 (50 mL)
  4. washThe organic layer was washed again with aqueous NaHCO3 (1×50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe resulting dirty yellow gum was purified by flash chromatography

Sources & evidence

ORD record
ord-00094fa3432546c4af53c96b371ce94b
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

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