Quinoline → HCID 23433500, compound

HRID 1604799Notes

Reaction equation

HRID 1604799 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:23])=[C:6]([C:8]2[C:9]([CH2:21][OH:22])=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH3:19])([CH3:18])[CH:12]=[C:11]3[CH3:20])[CH:7]=1.N1C2C(=CC=CC=2)C=CC=1.CC(C[AlH]CC(C)C)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:23][CH:21]([OH:22])[C:9]3[C:8]([C:6]=2[CH:7]=1)=[CH:17][CH:16]=[C:15]1[C:10]=3[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])([CH3:18])[NH:14]1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:23])=[C:6]([C:8]2[C:9]([CH2:21][OH:22])=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH3:19])([CH3:18])[CH:12]=[C:11]3[CH3:20])[CH:7]=1

Participants

6

Reactant 3

HCID 7047QuinolineHCID 14487Diisobutylaluminum hydrideHCID 23433500HCID 23433500, compound

Product 2

HCID 23433500HCID 23433500, compoundHCID 23433599HCID 23433599, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

(R/S)-9-Chloro-1,2-dihydro-5-methoxy-2,2,4-trimethyl-5H-chromono[3,4-f]quinoline (Compound 319, structure 47 of Scheme XIV, where R1 =H, R2 =chloro, R3 =methyl, X=O) (R/S)-9-chloro-1,2-dihydro-5-hydroxy-2,2,4-trimethyl-5H-chromono[3,4-f]quinoline (structure 46 of Scheme XIV, where R1 =H, R2 =chloro) and 6-(5-chloro-2-hydroxyphenyl)-1,2-dihydro-5-hydroxymethyl-2,2,4-trimethylquinoline (structure 94 of Scheme XXV, where R1-2 =R4-6 =H, R3 =chloro, R7-9 =methyl). Compound 209 (EXAMPLE 109) (100 mg, 0.307 mmol) was dissolved in THF, cooled to -40° C., and treated with DIBAL (614 μL, 0.614 mmol, 1 M in THF, Aldrich), warming to -20° C. over 30 min. The reaction mixture was quenched with NH4Cl (sat) (2 mL) and allowed to warm to rt. The reaction mixture was poured into a separatory funnel containing EtOAc and water. The aqueous was extracted with EtOAc (2×20 mL). The combined organics were washed with NaCl (sat) (1×15 mL), dried (Na2SO4), filtered, and concentrated onto Celite. The material was purified by flash chromatography using 25% EtOAc:hexanes to afford 65 mg of (R/S)-9-chloro-1,2-dihydro-5-hydroxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline (structure 46 of Scheme XIV, where R1 =H, R2 =chloro) and 20 mg of 6-(5-chloro-2-hydroxyphenyl)-1,2-dihydro-5-hydroxymethyl-2,2,4-trimethylquinoline (structure 94 of Scheme XXV, where R1-2 =R4-6 =H, R3 =chloro, R7-9 =methyl). Data for (R/S)-9-chloro-1,2-dihydro-5-hydroxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline: 1H NMR (400 MHz, acetone-d6) 7.71 (d, J=2.4, 1H), 7.55 (d, J=8.4, 1H), 7.11 (dd, J=8.5, 2.4 1H), 6.94 (d, J=8.4, 1H), 6.84 (d, J=5.9, 1H), 6.78 (d, J=8.2, 1H), 6.01 (d, J=6.0, 1H), 5.56 (bs, 1H), 5.52 (s, 1H), 2.36 (s, 3H), 1.31 (s, 3H), 1.18 (s, 3H). Data for 6-(5-chloro-2-hydroxyphenyl)-1,2-dihydro 5-hydroxymethyl-2,2,4-trimethylquinoline: 1H NMR (400 MHz, acetone-d6) 7.18 (dd, J=8.5, 3.0, 1H), 7.10 (d, J=2.5, 1H), 6.92 (d, J=8.6, 1H), 6.75 (d, J=8.0, 1H), 6.63 (d, J=8.1, 1H), 5.46 (s, 1H), 5.25 (s, 1H), 4.55 (ABq, J=11.4, 2H), 2.35 (s, 3H), 1.27 (s, 6H).

Workup

  1. temperaturewarming to -20° C. over 30 min
  2. customThe reaction mixture was quenched with NH4Cl (sat) (2 mL)
  3. temperatureto warm to rt
  4. additionThe reaction mixture was poured into a separatory funnel
  5. additioncontaining EtOAc and water
  6. extractionThe aqueous was extracted with EtOAc (2×20 mL)
  7. washThe combined organics were washed with NaCl (sat) (1×15 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated onto Celite
  11. customThe material was purified by flash chromatography

Sources & evidence

ORD record
ord-d9454ab4b9e242258601b4a16bf7a27a
Source dataset
uspto-grants-1999_11
Patent number
US05994544

Reaction notes

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