Water → 2-Bromo-5-(1,3-dioxan-2-yl)pyridine

HRID 1401318Notes

Reaction equation

HRID 1401318 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N:3]=1.[CH2:10](O)[CH2:11][CH2:12][OH:13].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.O>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[O:13][CH2:12][CH2:11][CH2:10][O:7]2)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 104421,3-PropanediolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 117692346-Bromo-3-pyridinecarboxaldehyde

Product 1

HCID 579672662-Bromo-5-(1,3-dioxan-2-yl)pyridineYield 84.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 6-bromopyridine-3-carbaldehyde (7) (25 g, 134 mmol) in toluene (130 mL) were added 1,3-propanediol (27) (20.45 g, 269 mmol) and 10-camphorsulfonic acid (3.12 g, 13.44 mmol). The reaction mixture was heated to reflux, with azeotropic removal of the evolved water, for 50 minutes, cooled down to r.t. and concentrated. The residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 solution (100 mL). Organic phase was collected and the aqueous phase was extracted with EtOAc (2×150 mL). Combined organic fractions were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to yield a brown solid which was triturated with Et2O and hexane (10/200 mL), to afford intermediate 28 (27.7 g, 84% yield) as a beige solid. MS (m/z): 244.1, 246.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.40 (d, J=2.4 Hz, 1H), 7.35 (dd, J=8.0, 2.4 Hz, 1H), 7.66 (dd, J=8.0, 0.4 Hz, 1H), 5.61 (s, 1H), 4.15 (ddd, J=11.8, 5.0, 1.2 Hz, 2H), 3.98-3.91 (m, 2H), 2.028-1.95 (m, 1H), 1.46 (d quint, J=13.2, 1.2 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. concentrationconcentrated
  3. customThe residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 solution (100 mL)
  4. customOrganic phase was collected
  5. extractionthe aqueous phase was extracted with EtOAc (2×150 mL)
  6. washCombined organic fractions were washed with brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a brown solid which
  11. customwas triturated with Et2O and hexane (10/200 mL)

Sources & evidence

ORD record
ord-1c16f9255a9149638e410d41148b6df3
Source dataset
uspto-grants-2014_12
Patent number
US08907091B2

Reaction notes

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