Water → (Rac)-2-{[8-(2,4-dichlorophenyl)-2,3,5,6-tetrahydro[1,4]oxazino[2,3,4-hi]indol-6-yl]methyl}-1h-isoindole-1,3(2h)-dione

HRID 2179906Notes

Reaction equation

HRID 2179906 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([O:11][CH2:12][CH2:13][N:7]3[CH2:6][CH:5]2[CH2:14][N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[CH:10]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[K+].[K+].O>C1COCC1.CC(N(C)C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([O:11][CH2:12][CH2:13][N:7]3[CH2:6][CH:5]2[CH2:14][N:15]2[C:16](=[O:25])[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:23]2=[O:24])[CH:10]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 2734659(2,4-Dichlorophenyl)boronic acid3×HCID 22488988(Rac)-2-[(8-iodo-2,3,5,6-tetrahydro[1,4]oxazino[2,3,4-hi]indol-6-yl)methyl]-1h-isoindole-1,3(2h)-dione

Product 1

HCID 22488987(Rac)-2-{[8-(2,4-dichlorophenyl)-2,3,5,6-tetrahydro[1,4]oxazino[2,3,4-hi]indol-6-yl]methyl}-1h-isoindole-1,3(2h)-dioneYield 32.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 69293768tetrahydrofuran N,N-dimethylacetamideSolvent

Conditions

Temperature
66 °C

Procedure

A mixture of (rac)-2-[(8-iodo-2,3,5,6-tetrahydro[1,4]oxazino[2,3,4-hi]indol-6-yl)methyl]-1H-isoindole-1,3(2H)-dione (0.044 g, 0.098 mmol), 2,4-dichlorophenylboronic acid (0.028 g, 0.147 mmol), tetrakis(triphenylphosphine)palladium (0.011 g, 0.01 mmol) and K2CO3 (0.054 g, 0.39 mmol) in THF-DMA (1:1, 2.0 mL) was heated at 66° C. for 2 h. 2,4-Dichlorophenylboronic acid (0.02 g, 0.105 mmol), tetrakis(triphenyl-phosphine)palladium (0.007 g, 0.006 mmol) and K2CO3 (0.02 g, 0.145 mmol) were added and heat was continued for 24 h. 2,4-Dichlorophenylboronic acid (0.02 g, 0.105 mmol) and tetrakis(triphenyl-phosphine)palladium (0.007 g, 0.006 mmol) were again added and heat was continued for another 3 h. After cooling down to rt, water (10.0 mL) and EtOAc (10.0 mL) were added and separated. The aqueous layer was extracted with EtOAc (2×). The combined EtOAc solution was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to prep TLC (EtOAc/hexane, 1:2) to give 0.015 g (32%) of colorless solid as the title compound: 1H NMR (400 MHz, CDCl3) δ 7.92-7.90 (m, 2 H), 7.81-7.78 (m, 2 H), 7.45 (d, J=2.0 Hz, 1 H), 7.27-7.18 (m, 2 H), 6.80 (s, 1 H), 6.74 (s, 1 H), 4.51-4.47 (m, 2 H), 4.13-4.09 (m, 1 H), 4.03-3.97 (m, 1 H), 3.83-3.79 (m, 1 H), 3.46-3.42 (m, 1 H), 3.38-3.35 (m, 1 H), 3.23-3.19 (m, 1 H), 3.16-3.14 (m, 1 H).

Workup

  1. temperatureheat
  2. temperatureheat
  3. waitwas continued for another 3 h
  4. temperatureAfter cooling down to rt
  5. customseparated
  6. extractionThe aqueous layer was extracted with EtOAc (2×)
  7. dry with materialThe combined EtOAc solution was dried over MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-e6700a9e472244afa5afa2b1340b7b80
Source dataset
uspto-grants-2005_05
Patent number
US06887868B2

Reaction notes

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