Potassium Carbonate → 3-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-propionic acid tert-butyl ester

HRID 920565Notes

Reaction equation

HRID 920565 reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][O:12][CH:11]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[Cl:29][C:30]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:31]=1[CH2:32]Br>CC#N>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][O:12][CH:11]([C:15]2[CH:16]=[CH:17][C:18]([O:21][CH2:32][C:31]3[C:30]([Cl:29])=[CH:37][CH:36]=[CH:35][C:34]=3[Cl:38])=[CH:19][CH:20]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 301591-Bromomethyl-2,6-dichlorobenzeneHCID 666540623-[2-(4-Hydroxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester

Product 1

HCID 670325163-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-propionic acid tert-butyl esterYield 97.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[2-(4-hydroxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester (5.00 g; 16.3 mmol) and K2CO3 (6.74 g; 48.8 mmol) in CH3CN (100 mL) was stirred for one hour at RT. Subsequently 2,6-dichlorobenzyl bromide (4.29 g; 17.9 mmol) was added and the resulting mixture was stirred overnight at RT. The reaction mixture was partitioned between EtOAc (250 mL) and 5% aqueous NaHCO3 solution (100 mL). The layers were separated and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O/hexanes 1:1) to afford 3-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-propionic acid tert-butyl ester (7.40 g).

Workup

  1. stirringthe resulting mixture was stirred overnight at RT
  2. customThe reaction mixture was partitioned between EtOAc (250 mL) and 5% aqueous NaHCO3 solution (100 mL)
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, Et2O/hexanes 1:1)

Sources & evidence

ORD record
ord-a7f10b2792004553a76f7de228d72e34
Source dataset
uspto-grants-2016_03
Patent number
US09273017B2

Reaction notes

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