Hydrochloric Acid → HCID 54521811, compound

HRID 987522Notes

Reaction equation

HRID 987522 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15](Br)[CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:48]([O:52][CH2:53][CH3:54])(=[O:51])[CH:49]=[CH2:50].Cl>C(N(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:50]=[CH:49][C:48]([O:52][CH2:53][CH3:54])=[O:51])[CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8821Ethyl Acrylate3×HCID 80271Tri-o-tolylphosphine2×HCID 53666838HCID 53666838, compound

Product 1

HCID 54521811HCID 54521811, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 7622TributylamineSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-benzyl-7-bromo-1,2,3,4-tetrahydro-quinoxaline-1-carboxylic acid tert-butyl ester (2.4 g, Reference Example 5), tri-o-tolylphosphine (96 mg), palladium(II) acetate (24 mg) and ethyl acrylate (1.3 ml) in tributylamine (20 ml) was heated to 110° C. After stirring for 2 hours at 110° C. the mixture was treated with further portions of ethyl acrylate (1.3 ml), tri-o-tolylphosphine (96 mg) and palladium(II) acetate (24 mg) and stirring was continued for a further 16 hours at 110° C. The mixture was then treated with ethyl acrylate (2.6 ml) and stirring was continued for a further 5 hours at 110° C. The reaction mixture was cooled to room temperature then acidified to pH 2 by addition of hydrochloric acid (50 ml, 1N) and then extracted three times with ethyl acetate (50 ml). The combined organic extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate (20 ml), then three times with water (20 ml), then dried over magnesium sulphate and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting brown oil (5 g) was subjected to flash chromatography on silica (0,040-0,063 mm) eluting with a mixture of cyclohexane and ethyl acetate (9:1, v/v) to give the title compound (1.83 g) as a yellow oil. 1H NMR, 400 MHz, (CD3)2SO: δ1.3 (t, 3H); 1.5 (s, 9H); 3.5 (broad t, 2H); 3.8 (broad t, 2H); 4.15 (q, 2H); 4.65 (s, 2H); 6.25 (d, J=16 Hz, 1H); 6.65 (d, J=8 Hz, 1H); 7.3 (m, 4H); 7.4 (t, 2H); 7.5 (d, J=16 Hz, 1H); 7.7 (broad s, 1H). MS (EI): M+ 422 (50%), 366 (60%), 322 (40%), 277 (20%), 231 (40%), 185 (10%), 157 (15%), 91 (100%), 57 (40%).

Workup

  1. stirringstirring
  2. waitwas continued for a further 16 hours at 110° C
  3. stirringstirring
  4. waitwas continued for a further 5 hours at 110° C
  5. temperatureThe reaction mixture was cooled to room temperature
  6. extractionextracted three times with ethyl acetate (50 ml)
  7. washThe combined organic extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate (20 ml)
  8. dry with materialthree times with water (20 ml), then dried over magnesium sulphate
  9. customevaporated under reduced pressure (2.7 kPa) at 40° C
  10. washeluting with a mixture of cyclohexane and ethyl acetate (9:1

Sources & evidence

ORD record
ord-15ba7876f0584bdabca806b045b26b6d
Source dataset
uspto-grants-2003_10
Patent number
US06632814B1

Reaction notes

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