Phenol → Methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate

HRID 369446Notes

Reaction equation

HRID 369446 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH3:15])=[CH:10][C:9]=2[OH:16])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26].C1(O)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C.C(#N)C>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH3:15])=[CH:10][C:9]=2[O:16][CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 996PhenolHCID 10340Sodium CarbonateHCID 11430Potassium Carbonate2×HCID 95576Methyl 2-bromopropionate2×HCID 232864162-(Morpholin-4-ylmethyl)-5-ethylphenol

Product 1

HCID 15483901Methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoateYield 93.1%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
70 °C

Procedure

To a 200 gallon reactor was added 582 pounds (%Wt/Wt Phenol to Solvent--14.1%) of acetonitrile, followed by 82 pounds (0. 323 mole--1.0 equiv.) of 87% pure 2-(morpholin-4-ylmethyl)-5-ethylphenol, 72.4 pounds (0.717 mole--2.22 equiv.) of triethylamine, and 99.0 pounds (0.717 mole--2.22 equiv.) of potassium carbonate. The mixture was heated to 70° C., and 90.1 pounds (0.539 mole--1.67 equiv.) of methyl 2-bromopropanoate was added during a two hour period a rate to maintain the reaction temperature at 65-70° C. Upon completion of addition, the reaction mixture was stirred at to 65-70° C. for seven hours. After this time, the reaction mixture was analyzed by GC, which indicated that 8% of the phenol starting material remained. An additional 9.0 pounds (0.054 mole--0.16 equiv.) of methyl 2-bromopropanoate, 8.0 pounds (0.058 mole--0.17 equiv.) of potassium carbonate, and 4.0 pounds (0.040 mole--0.12 equiv.) of triethylamine were added. Upon completion of addition, the reaction mixture is stirred at 65-70° C. for an additional hour. At the conclusion of this period, the reaction mixture is filtered, and the filtrate was concentrated under vacuum at 70° C. to yield an oil. The oil was taken up in 213 pounds of toluene and 185 pounds of a 2.5% aqueous sodium carbonate solution. The organic layer is separated from the aqueous layer and concentrated under vacuum at 90° C., yielding 106.0 pounds of 86.2% pure methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate (92% yield).

Workup

  1. temperatureto maintain the reaction temperature at 65-70° C
  2. additionUpon completion of addition
  3. additionUpon completion of addition
  4. stirringthe reaction mixture is stirred at 65-70° C. for an additional hour
  5. filtrationAt the conclusion of this period, the reaction mixture is filtered
  6. concentrationthe filtrate was concentrated under vacuum at 70° C.
  7. customto yield an oil
  8. customThe organic layer is separated from the aqueous layer
  9. concentrationconcentrated under vacuum at 90° C.

Sources & evidence

ORD record
ord-4809ec2567b142d5a558555b6df6e3f0
Source dataset
uspto-grants-2000_10
Patent number
US06136972

Reaction notes

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