4-Methylmorpholine → cis-4-[(4,6-Dihydro-4-oxo-3-phenylpyrido-[2,1-a]isoindol-1-yl)carbonyl]-2,6-dimethylmorpholine

HRID 1885347Notes

Reaction equation

HRID 1885347 reaction equation
[O:1]=[C:2]1[N:7]2[CH2:8][C:9]3[C:14]([C:6]2=[C:5]([C:15]([OH:17])=O)[CH:4]=[C:3]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3.[CH3:24][C@H:25]1[O:30][C@@H:29]([CH3:31])[CH2:28][NH:27][CH2:26]1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[O:1]=[C:2]1[N:7]2[CH2:8][C:9]3[C:14]([C:6]2=[C:5]([C:15]([N:27]2[CH2:26][C@H:25]([CH3:24])[O:30][C@H:29]([CH3:31])[CH2:28]2)=[O:17])[CH:4]=[C:3]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 516892Sodium BicarbonateHCID 6415002,6-Dimethylmorpholine, cis-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 156408234,6-Dihydro-4-oxo-3-phenylpyrido[2,1-a]isoindole-1-carboxylic acid

Product 1

HCID 22845717cis-4-[(4,6-Dihydro-4-oxo-3-phenylpyrido-[2,1-a]isoindol-1-yl)carbonyl]-2,6-dimethylmorpholine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 2.0 g of 4,6-dihydro-4-oxo-3-phenylpyrido[2,1-a]isoindole-1-carboxylic acid in 25 ml of N,N-dimethylformamide was treated under argon with 0.91 ml of cis-2,6-dimethylmorpholine and then with 0.81 ml of N-methylmorpholine and 2.8 g of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate and stirred at room temperature for a further 4.5 hours. The reaction mixture was then poured into a mixture of 50 ml of saturated sodium hydrogen carbonate solution and 250 ml of water. The crystallized-out crude product was filtered under suction and dried. After chromatography on silica gel with toluene and toluene/acetone (9:1) recrystallization was carried out twice from ethyl acetate. There was obtained 1.19 g of cis-4-[(4,6-dihydro-4-oxo-3-phenylpyrido-[2,1-a]isoindol-1-yl)carbonyl]-2,6-dimethylmorpholine as yellow crystals with a m.p. of 226°-228°.

Workup

  1. customThe crystallized-out crude product
  2. filtrationwas filtered under suction
  3. customdried
  4. customAfter chromatography on silica gel with toluene and toluene/acetone (9:1) recrystallization

Sources & evidence

ORD record
ord-07228cf5718f479a98c773385561ba88
Source dataset
uspto-grants-1992_09
Patent number
US05143912

Reaction notes

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