Diisopropylamine → HCID 22145899, compound

HRID 993268Notes

Reaction equation

HRID 993268 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:21])[C:19]=1[CH3:20].[CH:22]1([O:27][C:28]2[C:29]([O:38][CH3:39])=[N:30][CH:31]=[C:32]([CH:37]=2)[C:33](OC)=[O:34])[CH2:26][CH2:25][CH2:24][CH2:23]1.[Cl-].[NH4+]>O1CCCC1>[CH:22]1([O:27][C:28]2[CH:37]=[C:32]([C:33](=[O:34])[CH2:20][C:19]3[C:18]([Cl:21])=[CH:17][N:16]=[CH:15][C:14]=3[Cl:13])[CH:31]=[N:30][C:29]=2[O:38][CH3:39])[CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 109538273,5-Dichloro-4-methylpyridineHCID 22145812Methyl 5-(cyclopentyloxy)-6-methoxy-3-pyridinecarboxylateHCID 178418339Butyllithium

Product 1

HCID 22145899HCID 22145899, compoundYield 43.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (4.9 mL of a 2.5M solution in hexanes) is added dropwise to a stirred solution of diisopropylamine (1.7 mL) in dry tetrahydrofuran (20 mL) at −78° C. under a nitrogen atmosphere. After 30 minutes. a solution of 3,5-dichloro-4-methylpyridine (1.95 g) in dry tetrahydrofuran (10 mL) is added dropwise and the solution stirred at −78° C. for a further 30 minutes. A solution of methyl 5-cyclopentyloxy-6-methoxynicotinoate (1.5 g) in dry tetrahydrofuran (15 mL) is added and the red mixture stirred and allowed to warm to room temperature during 4 hours. After stirring overnight at room temperature the mixture is treated with saturated aqueous ammonium chloride. The tetrahydrofuran layer is separated and the aqueous phase is extracted with ethyl acetate. The combined organic layers are washed with saline and dried over anhydrous magnesium sulphate. Concentration gives a light brown oil which is triturated with a mixture of n-pentane and methyl t-butyl ether to give 1-(5-cyclopentyloxy-6-methoxypyridin-3-yl)-2-(3,5-dichloropyrid-4-yl)ethanone (1 g) in the form of a beige solid, m.p. 118-9° C. [Elemental analysis: C, 56.8; H, 4.82; Cl, 18.5; N, 7.40% calculated: C, 56.7; H, 4.76; Cl, 18.6; N, 7.35%.]

Workup

  1. stirringthe red mixture stirred
  2. temperatureto warm to room temperature during 4 hours
  3. stirringAfter stirring overnight at room temperature the mixture
  4. customThe tetrahydrofuran layer is separated
  5. extractionthe aqueous phase is extracted with ethyl acetate
  6. washThe combined organic layers are washed with saline
  7. dry with materialdried over anhydrous magnesium sulphate
  8. concentrationConcentration
  9. customgives a light brown oil which
  10. customis triturated with a mixture of n-pentane and methyl t-butyl ether

Sources & evidence

ORD record
ord-464e51f1cc3048838672701e3db20771
Source dataset
uspto-grants-2002_10
Patent number
US06472412B1

Reaction notes

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