Potassium Phosphate, Tribasic → methyl 7-(benzyloxy)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate

HRID 2410759Notes

Reaction equation

HRID 2410759 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[N:34]=[C:33](Br)[CH:32]=[C:31]([C:36]([O:38][CH3:39])=[O:37])[C:27]=3[NH:28][C:29]=2[CH:30]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[N:34]=[C:33]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=4)[CH:32]=[C:31]([C:36]([O:38][CH3:39])=[O:37])[C:27]=3[NH:28][C:29]=2[CH:30]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663026methyl 7-(benzyloxy)-2-bromo-5H-pyrido[3,2-b]indole-4-carboxylate

Product 1

HCID 66605153methyl 7-(benzyloxy)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylateYield 83.1%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of 3-(trifluoromethyl)phenylboronic acid (0.59 g, 3.1 mmol), methyl 7-(benzyloxy)-2-bromo-5H-pyrido[3,2-b]indole-4-carboxylate (1.07 g, 2.60 mmol), powdered potassium phosphate tribasic (1.33 g, 6.24 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.214 g, 0.520 mmol), and Pd(OAc)2 (0.058 g, 0.260 mmol) in a microwave vial was flushed with nitrogen. THF (13 mL) was added, the vial was capped, and the reaction was heated in a 70° C. oil bath for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with water and brine, dried with sodium sulfate, and the solvent removed. Silica gel chromatography (step gradient elution with DCM containing 50 to 25% hexane) afforded methyl 7-(benzyloxy)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.03 g, 2.16 mmol, 83% yield) as a tan solid. MS (ESI) m/z 477.1 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.47 (1H, s), 8.44 (1H, s), 8.30-8.37 (2H, m), 8.21 (1H, s), 7.57-7.67 (2H, m), 7.49 (2H, d, J=7.32 Hz), 7.42 (2H, t, J=7.48 Hz), 7.32-7.38 (1H, m), 7.03-7.09 (2H, m), 5.21 (2H, s), 4.10 (3H, s).

Workup

  1. customwas flushed with nitrogen
  2. additionTHF (13 mL) was added
  3. customthe vial was capped
  4. customIt was partitioned between EtOAc and water
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvent removed
  8. washSilica gel chromatography (step gradient elution with DCM containing 50 to 25% hexane)

Sources & evidence

ORD record
ord-1360234ac7b0408ba8de689a19b7c29d
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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