Hydrochloric Acid → 6-Hydroxymethyl-4-isobutyl-1,4-dihydro-quinoline-3-carbonitrile

HRID 1297671Notes

Reaction equation

HRID 1297671 reaction equation
[BH4-].[Li+].C([O:5][C:6]([C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][C:12]([C:18]#[N:19])=[C:11]2[CH2:20][CH:21]([CH3:23])[CH3:22])=O)C.Cl>CCOCC.CO.O>[OH:5][CH2:6][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]([C:18]#[N:19])[CH:11]2[CH2:20][CH:21]([CH3:23])[CH3:22]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 58585765HCID 58585765, compound

Product 1

HCID 585857716-Hydroxymethyl-4-isobutyl-1,4-dihydro-quinoline-3-carbonitrileYield 43.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To the suspension of lithium borohydride (93 mg, 4.3 mmol) and methanol (170 uL, 4.3 mmol) in ether (20 mL) was added the solution of 3-cyano-4-isobutyl-quinoline-6-carboxylic acid ethyl ester (example 46d, 600 mg, 2.1 mmol) in ether (5 mL). The mixture was stirred at reflux overnight. The mixture of water and methanol (v/v 1:1, 40 mL) was added to the above solution. Then 1 N HCl (3 mL) was added to quench the reaction. The product was extracted with ethylacetate. The combined organic layers were successively washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 5%-50% ethyl acetate in hexanes in 50 min) afforded 6-hydroxymethyl-4-isobutyl-1,4-dihydro-quinoline-3-carbonitrile (220 mg, 43%) as a yellow solid. LC-MS m/e 243 (MH+).

Workup

  1. temperatureat reflux overnight
  2. additionwas added to the above solution
  3. customto quench
  4. customthe reaction
  5. extractionThe product was extracted with ethylacetate
  6. washThe combined organic layers were successively washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d85056dfe1184f62b3f864f720d1d264
Source dataset
uspto-grants-2007_07
Patent number
US07250515B2

Reaction notes

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