Hydrochloric Acid → 4-(2-(4-Bromophenoxy)ethyl)morpholine
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.Cl.C([O-])([O-])=O.[K+].[K+]>C(#N)C.CCOCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1Participants
Procedure
The first step is a Williamson ether synthesis between 4-bromophenol (131 g) and N-chloroethylmorpholine (1 as the HCl salt; 141 g) using K2CO3 powder (3 to 3.5 equivalents) as the base and having acetonitrile as the solvent. The ingredients were mixed and stirred at reflux overnight with high conversion (96.3-99.1%). After dilution with dichloromethane and heptane, the reaction mixture was filtered and evaporated to give the desired product 2 in essentially a quantitative yield (216 g). Note that with similar substrates (e.g., 4-bromo-3-fluorophenol), conversions (even with extensive heating) were not always so high (e.g., 59.9-98.3%). Both the alkyl chloride and the K2CO3 are preferably purchased from Aldrich. If continued heating does not drive reaction to completion, unreacted bromophenol can readily be removed by dissolving the crude reaction mixture in 4 parts toluene and washing out the phenol with 4 parts 15% aqueous NaOH.
Workup
- additionThe ingredients were mixed
- temperatureat reflux overnight with high conversion (96.3-99.1%)
- filtrationAfter dilution with dichloromethane and heptane, the reaction mixture was filtered
- customevaporated
Sources & evidence
- ORD record
- ord-3228296a244d424dabc1c152372c9d86
- Source dataset
- uspto-grants-2011_05
- Patent number
- US07939529B2
Reaction notes
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