Morpholine → [5-Hydroxy-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-morpholin-4-yl-methanone

HRID 132814Notes

Reaction equation

HRID 132814 reaction equation
C(O[C:4]([C:6]1[N:7]([CH2:16][C:17]([F:20])([F:19])[F:18])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[CH:10][CH:9]=2)=[O:5])C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1.C(N(C(C)C)C(C)C)C>CN(C)C=O.C(OCC)(=O)C>[OH:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:16][C:17]([F:18])([F:19])[F:20])[C:6]([C:4]([N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1)=[O:5])=[CH:14]2

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 24985291Ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate2×

Product 1

HCID 67527268[5-Hydroxy-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-morpholin-4-yl-methanoneYield 74%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-hydroxy-1-(2,2,2-trifluoro-ethyl)-1H-indole-2-carboxylic acid (intermediate 1, step c, 7.62 g, 1.0 eq.), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (12.8 g, 1.3 eq.), morpholine (3.36 mL, 1.3 eq.) and N-ethyldiisopropylamine (25.7 mL, 5 eq.) in dimethylformamide (85 mL) was stirred at room temperature for 24 h. The reaction mixture was diluted with ethyl acetate and washed with hydrochloric acid (1N), water and brine and dried over sodium sulfate, filtered and concentrated in vacuo. The precipitate was filtered, washed with ethyl acetate and dried in vacuo to yield 7.15 g (74%) of the desired product as off-white solid. MS (m/e): 329.5 (MH+, 100%).

Workup

  1. washwashed with hydrochloric acid (1N), water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. filtrationThe precipitate was filtered
  6. washwashed with ethyl acetate
  7. customdried in vacuo

Sources & evidence

ORD record
ord-cd9cf0bdd10443b58313a72cb9ca7454
Source dataset
uspto-grants-2008_06
Patent number
US07388095B2

Reaction notes

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