Acetone → 2-(6-Bromopyridin-2-yl)propan-2-ol

HRID 1396461Notes

Reaction equation

HRID 1396461 reaction equation
CCCCCC.Br[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Br:14])[N:9]=1.C(=O)=O.[CH3:18][C:19](=[O:21])[CH3:20].[Cl-].[NH4+]>C1COCC1>[Br:14][C:10]1[N:9]=[C:8]([C:19]([OH:21])([CH3:20])[CH3:18])[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 5

HCID 180AcetoneHCID 280Carbon Dioxide2×HCID 8058HexaneHCID 122742,6-DibromopyridineHCID 25517Ammonium Chloride

Product 1

HCID 227143012-(6-Bromopyridin-2-yl)propan-2-olYield 94.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-76 °C

Procedure

A dry 250 mL round bottomed flask fitted with a stir bar and septum was charged with n-buthyllithium 1.6 M in hexane (30.3 mL, 48.5 mmol), the flask was cooled in a dry-ice acetone bath to −76° C. and added THF (30 mL) to the solution, then added a solution of 2,6-dibromopyridine (11.5 g, 48.5 mmol) in THF (60 mL) slowly via cannula over 15 min. The dark yellow-brown solution was stirred for 30 minutes in the dry-ice bath, then added propan-2-one (4.75 g, 6 mL, 81.7 mmol). The deep green solution was stirred in the dry-ice bath for 15 minutes and then allowed to warm to room temperature. After an hour, added carefully a saturated aqueous solution of ammonium chloride (100 mL) and product extracted with dichloromethane (3×200), combined organics dried over magnesium sulfate and evaporated. The residue was purified by flash chromatography (silica gel 50 μm, 150 g, Analogix) eluting with 0 to 50% over 20 min dichloromethane/hexanes, obtained 2-(6-bromopyridin-2-yl)propan-2-ol (9.9 g, 94.3% yield) as a light yellow clear liquid. 1H NMR (CHLOROFORM-d) δ: 7.52-7.59 (m, 1H), 7.33-7.40 (m, 2H), 4.05 (br. s., 1H), 1.55 (s, 6H); LC-MS 216.1, 218.1 [M+H]+.

Workup

  1. customA dry 250 mL round bottomed flask fitted with a stir bar
  2. temperatureto warm to room temperature
  3. waitAfter an hour
  4. extractionextracted with dichloromethane (3×200)
  5. dry with materialcombined organics dried over magnesium sulfate
  6. customevaporated
  7. customThe residue was purified by flash chromatography (silica gel 50 μm, 150 g, Analogix)
  8. washeluting with 0 to 50% over 20 min dichloromethane/hexanes

Sources & evidence

ORD record
ord-183071a9e89f4e8b91ecb6116bea5ff6
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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