Acetaldehyde → 6-Chloro-α-methyl-5-(phenylmethoxy)-2-pyridinemethanol

HRID 1637787Notes

Reaction equation

HRID 1637787 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[C:4](I)[N:3]=1.C([Li])CCC.[CH:22](=[O:24])[CH3:23]>C1COCC1>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[C:4]([CH:22]([OH:24])[CH3:23])[N:3]=1

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 18799610HCID 18799610, compoundHCID 178418339Butyllithium

Product 1

HCID 187996156-Chloro-α-methyl-5-(phenylmethoxy)-2-pyridinemethanolYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

2-Chloro-3-benzyloxy-6-iodo-pyridine (416 mg, 1.2 mmol) in THF (4 mL) was cooled to -78° C. and treated with n-butyllithium (1.2 mL of 1.6M in hexanes, 1.92 mmol). After 60 minutes, acetaldehyde (237 mg, 5.4 mmol) was added and the reaction was allowed to warm to 22° C. over 2 hours. The reaction was quenched with water (5 mL) and concentrated in vacuo. The remaining solution was extracted several times with ethyl acetate, dried over MgSO4, and concentrated in vacuo to yield an oil. The oil was chromatographed 1:1 hexane/ethyl acetate to yield 220 mg (70%) of 2-chloro-3-benzyloxy-6-(1-hydroxyethyl)-pyridine.

Workup

  1. customThe reaction was quenched with water (5 mL)
  2. concentrationconcentrated in vacuo
  3. extractionThe remaining solution was extracted several times with ethyl acetate
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto yield an oil
  7. customThe oil was chromatographed 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-cdde08c87f99446c8162444151a832d7
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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