Trifluoroacetic acid → ethyl 6-[(ethoxycarbonyl)amino]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

HRID 1789983Notes

Reaction equation

HRID 1789983 reaction equation
[CH2:1]([O:3][C:4]([NH:6][C:7]1[C:15]2[NH:14][C:13]3[CH2:16][CH2:17][N:18]([C:20]([O:22][C:23](C)(C)[CH3:24])=[O:21])[CH2:19][C:12]=3[C:11]=2[CH:10]=[CH:9][CH:8]=1)=[O:5])[CH3:2].C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+].ClC(OCC)=O>C(Cl)Cl.O>[CH2:1]([O:3][C:4]([NH:6][C:7]1[C:15]2[NH:14][C:13]3[CH2:16][CH2:17][N:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:19][C:12]=3[C:11]=2[CH:10]=[CH:9][CH:8]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 22036756tert-butyl 6-[(ethoxycarbonyl)amino]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

Product 1

HCID 22036763ethyl 6-[(ethoxycarbonyl)amino]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 6-[(ethoxycarbonyl)amino]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate (8.7 g, 24.3 mmol) in CH2Cl2 (40 mL) at rt was added TFA (20 mL) and stirred at rt for 3 hours before the solvent was removed by the nitrogen stream. The solution was diluted with water (30 mL) and extracted with CH2Cl2 (2×30 mL). The combined extracts were dried over magnesium sulfate, and concentrated to afford an crude residue that was re-dissolved in CH2Cl2 (40 mL) followed by saturated K2CO3 (30 mL), ethyl chloroformate (2.4 mL, 4.0 mmol) and stirred at 25° C. for 0.5 hour. The solution was diluted with water (30 mL) and extracted with CH2Cl2 (2×30 mL). The combined extracts were dried over magnesium sulfate, concentrated, and purified by flash chromatography to afford ethyl 6-[(ethoxycarbonyl)amino]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate (4.5 g, 67%) as a clear oil. MS [M+H]+ 332. 1H NMR (CDCl3, 300 MHz): δ 7.00 (t, 1H, J=7.7 Hz), 6.82 (m, 1H), 6.71 (m, 1H), 4.62 (s, 2H), 4.02–4.31 (m, 4H), 3.82 (t, 1H, J=5.5 Hz), 2.82 (t, 1H, J=5.5 Hz), 1.20–1.24 (m, 6H) ppm.

Workup

  1. customwas removed by the nitrogen stream
  2. additionThe solution was diluted with water (30 mL)
  3. extractionextracted with CH2Cl2 (2×30 mL)
  4. dry with materialThe combined extracts were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto afford an crude residue that
  7. stirringstirred at 25° C. for 0.5 hour
  8. extractionextracted with CH2Cl2 (2×30 mL)
  9. dry with materialThe combined extracts were dried over magnesium sulfate
  10. concentrationconcentrated
  11. custompurified by flash chromatography

Sources & evidence

ORD record
ord-5401a6a99e0e4a08b9bdab2e0357f4c7
Source dataset
uspto-grants-2006_07
Patent number
US07071186B2

Reaction notes

Loading…