Diisobutylaluminum hydride → HCID 23433500, compound

HRID 1939563Notes

Reaction equation

HRID 1939563 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH:9]([OH:23])[C:10]3[C:19]([C:4]=2[CH:3]=1)=[CH:18][CH:17]=[C:16]1[C:11]=3[C:12]([CH3:22])=[CH:13][C:14]([CH3:21])([CH3:20])[NH:15]1.CC(C[AlH]CC(C)C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH:9]([OH:23])[C:10]3[C:19]([C:4]=2[CH:3]=1)=[CH:18][CH:17]=[C:16]1[C:11]=3[C:12]([CH3:22])=[CH:13][C:14]([CH3:20])([CH3:21])[NH:15]1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:19]2[C:10]([CH2:9][OH:23])=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14]([CH3:21])([CH3:20])[CH:13]=[C:12]3[CH3:22])[CH:3]=1

Participants

5

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 23433599HCID 23433599, 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-hydroxy-2,2,4-trimethy1-5H-chromeno[3,4-f]quinoline (structure 46 of Scheme XIV, where R1 =H, R2 =chloro) and 6-(5-chloro-2-hydroxyphenyD-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 gL, 0.614 mmol, 1M 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-)1,2dihydro-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-4419083594f545c2b7bd1a57c0f6a45b
Source dataset
uspto-grants-1997_12
Patent number
US05696133

Reaction notes

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