1-Hydroxybenzotriazole → tert-butyl (2R)-2-[(cyclopropyl{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}amino)carbonyl]morpholine-4-carboxylate

HRID 922417Notes

Reaction equation

HRID 922417 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[C:12]2[CH:13]=[CH:14][O:15][C:11]=2[CH:10]=[C:9]([CH:16]([NH:18][CH:19]2[CH2:21][CH2:20]2)[CH3:17])[CH:8]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][C@@H:31]([C:35](O)=[O:36])[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:19]1([N:18]([CH:16]([C:9]2[CH:8]=[C:7]([O:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:12]3[CH:13]=[CH:14][O:15][C:11]=3[CH:10]=2)[CH3:17])[C:35]([C@@H:31]2[O:32][CH2:33][CH2:34][N:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:30]2)=[O:36])[CH2:20][CH2:21]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6559076(2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 68309919HCID 68309919, compound

Product 1

HCID 68309685tert-butyl (2R)-2-[(cyclopropyl{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}amino)carbonyl]morpholine-4-carboxylateYield 88.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}-cyclopropanamine (200 mg) and (2R)-4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (240 mg) in N,N-dimethylformamide (7 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (212 mg) and 1-hydroxybenzotriazole (140 mg) under ice-cooling, and then stirred at room temperature for 18 hours. To the reaction mixture was added aqueous saturated sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with water, 10% aqueous citric acid solution and saturated saline, and then concentrated under reduced pressure to give tert-butyl (2R)-2-[(cyclopropyl{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}amino)carbonyl]morpholine-4-carboxylate [Ex(161-1)] (306 mg) as a yellow oil.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was sequentially washed with water, 10% aqueous citric acid solution and saturated saline
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4c570cddb6554540bf1d77a1f4f22a21
Source dataset
uspto-grants-2016_03
Patent number
US09278944B2

Reaction notes

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