Acetic Acid → ethyl 6-(2,3-dihydro-1H-inden-2-ylamino)-2-methyl-4-phenylquinoline-3-carboxylate

HRID 570387Notes

Reaction equation

HRID 570387 reaction equation
CC(O)=O.[NH2:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([CH3:16])[C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:9]2[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH2:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][C:29]1=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH2:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH:29]1[NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([CH3:16])[C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:9]2[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 119832-IndanoneHCID 5049666Sodium triacetoxyborohydride2×HCID 68294637Ethyl 6-amino-2-methyl-4-phenylquinoline-3-carboxylate

Product 1

HCID 68294031ethyl 6-(2,3-dihydro-1H-inden-2-ylamino)-2-methyl-4-phenylquinoline-3-carboxylateYield 75.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A method of Abdel-Magid et al (J. Org. Chem., 61, 3849, 1996) was used: Glacial AcOH (0.25 ml) was added to a solution of the product of Step 2 (1.46 g, 4.4 mmol), 1H-inden-2(3H)-one (0.46 g, 4.5 mmol) and NaBH(OAc)3 (1.4 g, 6.55 mmol) in anhydrous 1,2-dichloroethane (17 ml). The resulting mixture was stirred overnight at room temperature under N2 and to it more of NaBH(OAc)3 (0.4 g, 1.9 mmol) was added. After 2 h of stirring at room temperature, the mixture was quenched by addition of 1N NaOH aq (5 ml). This was diluted to 60 ml with Et2O and washed with H2O and brine. The organic phase was dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography (SiO2, CH2Cl2) to give pure product as a creamy solid (1.4 g, 71%). 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=9.0 Hz, 1H), 7.34-7.5(m, 5H), 7.12-7.21(m, 4H), 7.05(dd, J=2.6, 9.0 Hz, 1H), 6.49(d, J=2.6 Hz, 1H), 4.17(m, 1H), 4.08(m, 1H), 3.19-3.27(m 2H), 2.73-2.83(m, 2H), 2.7(s, 3H), 1.22(s, 9H).

Workup

  1. additionwas added
  2. customthe mixture was quenched by addition of 1N NaOH aq (5 ml)
  3. additionThis was diluted to 60 ml with Et2O
  4. washwashed with H2O and brine
  5. dry with materialThe organic phase was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customfiltrate evaporated to dryness under reduced pressure
  8. customThe residue was purified by flash column chromatography (SiO2, CH2Cl2)

Sources & evidence

ORD record
ord-72f2338ac22e46f6954c2b209f6fcd7a
Source dataset
uspto-grants-2015_05
Patent number
US09023848B2

Reaction notes

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