4-Methylmorpholine → HCID 66705899, compound

HRID 2276387Notes

Reaction equation

HRID 2276387 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:52][C:53]([F:66])([F:65])[CH2:54][O:55][C:56]1[CH:64]=[CH:63][C:59]([C:60](O)=[O:61])=[CH:58][N:57]=1>C1COCC1.CCOC(C)=O>[F:66][C:53]([F:52])([F:65])[CH2:54][O:55][C:56]1[CH:64]=[CH:63][C:59]([C:60]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]3)=[CH:4][CH:3]=2)=[O:61])=[CH:58][N:57]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27810286-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acidHCID 66705988(S)-Tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate

Product 1

HCID 66705899HCID 66705899, compoundYield 81.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of (S)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (1.5 g) in THF (75 ml) were added sequentially N-methylmorpholine (1.78 ml), HBTU (3.07 g) and 6-(2,2,2-trifluoroethoxy)nicotinic acid (1.63 g) and the mixture was stirred at room temperature for 17 h. The suspension was diluted with EtOAc and washed sequentially with 0.5 M aq. HCl, sat. aq. NaHCO3 and saturated brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by recrystallisation from heptane/EtOAc (1:1) to give (S)-tert-butyl 2-(4-(6-(2,2,2-trifluoroethoxy)nicotinamido)phenyl)morpholine-4-carboxylate (2.11 g, 81%) as a white solid. MS (ISP): 482.1 ([M+H]+).

Workup

  1. washwashed sequentially with 0.5 M aq. HCl, sat. aq. NaHCO3 and saturated brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by recrystallisation from heptane/EtOAc (1:1)

Sources & evidence

ORD record
ord-a59daf5348cd46a884ae7a34409c22c8
Source dataset
uspto-grants-2015_09
Patent number
US09132136B2

Reaction notes

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