Acetone → Methyl 2-[[4-[2-(benzyloxymethoxy)ethyl]phenyl]amino]-2-methylpropionate

HRID 1006457Notes

Reaction equation

HRID 1006457 reaction equation
[CH2:1]([O:8][CH2:9][O:10][CH2:11][CH2:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH2:20].Cl[C:22](Cl)(Cl)[C:23]([CH3:26])(O)[CH3:24].[OH-].[K+].C[C:32](C)=[O:33]>>[CH2:1]([O:8][CH2:9][O:10][CH2:11][CH2:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:23]([CH3:26])([CH3:24])[C:22]([O:33][CH3:32])=[O:20])=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 180AcetoneHCID 14797Potassium HydroxideHCID 122198322-Propanol, 1,1,1-trichloro-2-methyl-, hydrateHCID 226719344-[2-(Benzyloxymethoxy)ethyl]aniline

Product 1

HCID 22671927Methyl 2-[[4-[2-(benzyloxymethoxy)ethyl]phenyl]amino]-2-methylpropionate

Procedure

To a stirred solution of 4-[2-(benzyloxymethoxy)-ethyl]aniline (1.4 g) and 1,1,1-trichloro-2-methyl-2-propanol hydrate (2.0 g) in acetone (10 ml) was added potassium hydroxide (2.9 g) three times (total 8.7 g) at intervals of 10 minutes under ice-cooling, and the mixture was stirred for 21 hours at room temperature. After the reaction mixture was concentrated under reduced pressure, the residue was dissolved in ice-water and washed with diethyl ether. The aqueous layer was neutralized with 2N hydrochloric acid, and the solvent was removed under reduced pressure. The residue was dissolved in a mixed solvent of dichloromethane (10 ml) and methanol (5.0 ml), a solution of diazomethane in diethyl ether was added until the reaction solution was colored, and the mixture was stirred for 3 hours at room temperature. After the reaction mixture was concentrated under reduced pressure, purification of the residue by flash column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1) gave methyl 2-[[4-[2-(benzyl-oxymethoxy)ethyl]phenyl]amino]-2-methylpropionate (888 mg).

Workup

  1. temperaturecooling
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in ice-water
  4. washwashed with diethyl ether
  5. customthe solvent was removed under reduced pressure
  6. dissolutionThe residue was dissolved in a mixed solvent of dichloromethane (10 ml) and methanol (5.0 ml)
  7. additiona solution of diazomethane in diethyl ether was added until the reaction solution
  8. stirringthe mixture was stirred for 3 hours at room temperature
  9. concentrationAfter the reaction mixture was concentrated under reduced pressure, purification of the residue by flash column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-616dfafcfa574d3ea2787a00084cc332
Source dataset
uspto-grants-2004_09
Patent number
US06790865B2

Reaction notes

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