Diisopropylamine → HCID 22145873, compound

HRID 1994351Notes

Reaction equation

HRID 1994351 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:33]([O:34][CH3:35])=[CH:32][N:31]=[C:30]([CH:36]=[O:37])[CH:29]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1>O1CCCC1.[Cl-].[NH4+]>[CH:22]1([O:27][C:28]2[C:33]([O:34][CH3:35])=[CH:32][N:31]=[C:30]([CH:36]([OH:37])[CH2:20][C:19]3[C:18]([Cl:21])=[CH:17][N:16]=[CH:15][C:14]=3[Cl:13])[CH:29]=2)[CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 109538273,5-Dichloro-4-methylpyridineHCID 15453395HCID 15453395, compoundHCID 178418339Butyllithium

Product 1

HCID 22145873HCID 22145873, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Procedure

n-Butyllithium (3.21 mL of 2.5 M solution) is added to a solution of diisopropylamine (1.15 mL) in dry tetrahydrofuran (25 mL) with the temperature being maintained below −60° C. After 30 min a solution of 3,5-dichloro-4-methylpyridine (1.21 g) in tetrahydrofuran (7 mL) is added dropwise and the mixture stirred for a further 30 min. A solution of 4-cyclopentyloxy-5-methoxypyridine-2-carboxaldehyde (1.65 g) in tetrahydrofuran (7 mL) is added and the mixture stirred for 4 hours whilst being allowed to warm to room temperature. After a further 18 hours at room temperature the mixture is diluted with saturated aqueous ammonium chloride (50 mL) and extracted with ethyl acetate. The extracts are washed with water, dried (MgSO4) and evaporated to give a yellow oil. The oil is triturated with n-pentane to give (±)-1-(4-cyclopentyloxy-5-methoxypyridin-2-yl)-2-(3,5-dichloropyridin-4-yl)ethanol (1.4 g) as an off-white solid, m.p. 110-112° C. [1Hnmr in D6-DMSO shifts relative to Me4Si:— 1.55-1.78, 6H, m; 1.95, 2H, m; 3.27, 2H, m; 3.79, 3H, s; 4.89, 2H, m; 5.64, 1H, d; 7.07, 1H, s; 7.98, 1H s; 8.54, 2H, s.].

Workup

  1. temperaturebeing maintained below −60° C
  2. stirringthe mixture stirred for 4 hours
  3. extractionextracted with ethyl acetate
  4. washThe extracts are washed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give a yellow oil
  8. customThe oil is triturated with n-pentane

Sources & evidence

ORD record
ord-6927db60c9ad4982bae4e40728b44814
Source dataset
uspto-grants-2010_01
Patent number
US07652144B2

Reaction notes

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