Hydrochloric Acid → 1-{3-[3-Bromo-4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidine

HRID 251441Notes

Reaction equation

HRID 251441 reaction equation
C([Li])CCC.CCCCCC.[CH3:12][C:13]1([CH3:34])[CH2:17][O:16][C:15]([C:18]2[CH:33]=[CH:32][C:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:20][CH:19]=2)=[N:14]1.[Br:35]Br.Cl>O1CCCC1>[Br:35][C:33]1[CH:32]=[C:21]([CH:20]=[CH:19][C:18]=1[C:15]1[O:16][CH2:17][C:13]([CH3:34])([CH3:12])[N:14]=1)[O:22][CH2:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8058HexaneHCID 24408BromineHCID 117024471-{3-[4-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidineHCID 178418339Butyllithium

Product 1

HCID 119521521-{3-[3-Bromo-4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 2.1 M solution of n-butyllithium in hexane (580 μl, 2 eq, 1.28 mmol) is added dropwise to a solution of 1-{3-[4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidine 1 (200 mg, 0.64 mmol, 1 eq) in cold (0° C.) tetrahydrofuran (10 ml), and the resulting solution is stirred 4 hours at 0° C. Bromine (64 μL, 2 eq, 1.28 mmol) is then added and the mixture is left to stir at 22° C. overnight. The solution is then poured into 5 ml of 0.1 N aqueous hydrogen chloride and extracted with ether. The aqueous layer is then made basic (pH 10) with 5 N sodium hydroxide and extracted with dichloromethane. The chlorinated solution is then dried over magnesium sulfate, concentrated under reduced pressure. 1-{3-[3-bromo-4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidine 17 is separated from the remaining starting material by careful chromatography over silicagel (dichloromethane/methanol, gradient).

Workup

  1. waitthe mixture is left
  2. stirringto stir at 22° C. overnight
  3. extractionextracted with ether
  4. extractionextracted with dichloromethane
  5. dry with materialThe chlorinated solution is then dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. custom1-{3-[3-bromo-4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenoxy]propyl}piperidine 17 is separated from the

Sources & evidence

ORD record
ord-e09149bec23641b697f855165e2272ee
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

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