Hydrochloric Acid → 2-Bromo-α-(2-chlorophenyl)-3-pyridinemethanol

HRID 2251954Notes

Reaction equation

HRID 2251954 reaction equation
[Li+].CC([N-]C(C)C)C.[Br:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=[O:20].Cl>C1COCC1>[Br:9][C:10]1[C:15]([CH:19]([C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[Cl:16])[OH:20])=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 69962-ChlorobenzaldehydeHCID 79732-BromopyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 866012412-Bromo-α-(2-chlorophenyl)-3-pyridinemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add LDA (400 mL, 0.8 mol) to 2-bromopyridine (105 g, 0.667 mol) in THF (3.2 L) at −78° C. and stir. After 2 hours, add 2-chlorobenzaldehyde (103 g, 0.733 mol) in THF (300 mL) and allow the reaction mixture to gradually warm to ambient temperature. Treat the reaction mixture with 1 M HCl (1.7 L) and extract with diethyl ether. Combine the organic layers and wash with water and brine. Dry over sodium sulfate, filter, and concentrate under reduced pressure. Purification by flash chromatography, eluting with hexane:ethyl acetate (10:1 to 1:1) gives the title compound: 1H NMR (300 MHz, CDCl3), δ8.28(dd, 1H, J=1.83, 4.73), 7.67 (dd, 1H, J=1.83, 7.63), 7.48-7.19 (m, 5H), 6.41 (s, 1H), 3.10 (bs, 1H); MS (IS) m/z 298.0 (M+1), 300.0 (M+1); Analysis for C12H9BrClNO: calcd: C, 48.27; H, 3.04; N, 4.69; found: C, 49.06; H, 3.18; N, 4.64. Rf=0.29 heptane: ethyl acetate, 2:1).

Workup

  1. extractionextract with diethyl ether
  2. washwash with water and brine
  3. dry with materialDry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customPurification by flash chromatography
  7. washeluting with hexane:ethyl acetate (10:1 to 1:1)

Sources & evidence

ORD record
ord-a9949d77e28042d4a6cc230155e38c81
Source dataset
uspto-grants-2008_01
Patent number
US07320994B2

Reaction notes

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