Diethyl Ether → [8-(4-Methoxy-phenyl)-1,4-dioxa-spiro[4.5]dec-8-yl]-dimethylamine

HRID 76942Notes

Reaction equation

HRID 76942 reaction equation
CCOCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[CH3:15][N:16]([CH3:29])[C:17]1(C#N)[CH2:26][CH2:25][C:20]2([O:24][CH2:23][CH2:22][O:21]2)[CH2:19][CH2:18]1>C1COCC1>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([C:17]2([N:16]([CH3:29])[CH3:15])[CH2:26][CH2:25][C:20]3([O:24][CH2:23][CH2:22][O:21]3)[CH2:19][CH2:18]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 3283Diethyl Ether3×HCID 77304-BromoanisoleHCID 3609778-(Dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 12595623[8-(4-Methoxy-phenyl)-1,4-dioxa-spiro[4.5]dec-8-yl]-dimethylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Magnesium (3.65 g, 150 mmol) and an iodine crystal were provided in a nitrogen atmosphere and heated. Abs. ether (10 mL) was then added and a solution of 4-bromoanisole (18.8 mL, 150 mmol) in abs. ether (150 mL) was added in drops so that the ether lightly boiled. The solution formed was subsequently stirred for 1 h at RT and then mixed in drops with a solution of 8-dimethylamino-1,4-dioxa-spiro[4.5]decane-8-carbonitrile (10.5 g, 50.0 mmol) in abs. THF (100 mL), and the solution heated to 37-40° C. until boiling during the addition. A precipitate separated out and the batch was stirred overnight at RT. The solution was mixed with NH4Cl solution with ice cooling, the phases were separated, the aqueous phase extracted three times with ether, the combined organic phases washed with saturated NaCl solution and water, dried over Na2SO4 and concentrated to low volume in a vacuum. Flash chromatography of the residue with ethyl acetate/methanol (20:1→9:1→4:1→1:4→MeOH) gave the desired product.

Workup

  1. temperatureheated
  2. customThe solution formed
  3. additionuntil boiling during the addition
  4. customA precipitate separated out
  5. stirringthe batch was stirred overnight at RT
  6. additionThe solution was mixed with NH4Cl solution with ice cooling
  7. customthe phases were separated
  8. extractionthe aqueous phase extracted three times with ether
  9. washthe combined organic phases washed with saturated NaCl solution and water
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated to low volume in a vacuum

Sources & evidence

ORD record
ord-0b7058a64305471889a3fe33391edd32
Source dataset
uspto-grants-2014_09
Patent number
US08835689B2

Reaction notes

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