Aluminium lithium hydride → 1,1-dimethylethyl 4-(3,4-dichlorophenyl)-5-(hydroxymethyl)-2-methyl-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 639848Notes

Reaction equation

HRID 639848 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:14][CH:13]([CH3:15])[N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:10]=2[C:23](OCC)=[O:24])[CH:5]=[CH:6][C:7]=1[Cl:8].ClC1C=C(C2CCN(C(OC(C)(C)C)=O)C(C)C=2C(OCC)=O)C=CC=1Cl.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:14][CH:13]([CH3:15])[N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:10]=2[CH2:23][OH:24])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 21226445Aluminium lithium hydrideHCID 59255992HCID 59255992, compoundHCID 592560481-(1,1-dimethylethyl) 3-ethyl 4-(3,4-dichlorophenyl)-2-methyl-5,6-dihydro-1,3(2H)-pyridinedicarboxylate

Product 1

HCID 592560311,1-dimethylethyl 4-(3,4-dichlorophenyl)-5-(hydroxymethyl)-2-methyl-3,6-dihydro-1(2H)-pyridinecarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A mixture of regioisomers 1-(1,1-dimethylethyl) 3-ethyl 4-(3,4-dichlorophenyl)-6-methyl-5,6-dihydro-1,3(2H)-pyridinedicarboxylate and 1-(1,1-dimethylethyl) 3-ethyl 4-(3,4-dichlorophenyl)-2-methyl-5,6-dihydro-1,3(2H)-pyridinedicarboxylate (P21, 0.45 g) was dissolved in toluene (15 mL) and cooled to −20° C. Lithium aluminium hydride 1.0M in THF (0.869 mL) was added dropwise at −20° C. and the mixture was stirred at this temperature for 2 h. The reaction was then quenched with a saturated solution of NH4Cl (10 mL) and diluted with ethyl acetate (20 mL); the organic layer was separated, washed with water (20 mL), dried and concentrated in vacuo. Purification by chromatography on silica gel eluting with a gradient 100% cyclohexane-50% cyclohexane/ethyl acetate afforded 240 mg of title compound as colourless oil. The structure of the major regioisomer was confirmed by nOe NMR experiments.

Workup

  1. customThe reaction was then quenched with a saturated solution of NH4Cl (10 mL)
  2. additiondiluted with ethyl acetate (20 mL)
  3. customthe organic layer was separated
  4. washwashed with water (20 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography on silica gel eluting with a gradient 100% cyclohexane-50% cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-31f83b3ec4ff497195ae0592ee9a4a49
Source dataset
uspto-grants-2010_04
Patent number
US07691893B2

Reaction notes

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