Water → 3-(3-Benzyloxy-4-fluoro-phenylamino)-but-2-enoic acid ethyl ester

HRID 2415499Notes

Reaction equation

HRID 2415499 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH2:16])[CH:12]=[CH:13][C:14]=1[F:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:18][C:19]([CH3:21])=O.O.C([O-])(O)=O.[Na+]>C1CCCCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:24]([O:23][C:17](=[O:22])[CH:18]=[C:19]([NH:16][C:11]1[CH:12]=[CH:13][C:14]([F:15])=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:10]=1)[CH3:21])[CH3:25]

Participants

7

Reactant 4

HCID 962WaterHCID 8868Ethyl AcetoacetateHCID 516892Sodium BicarbonateHCID 226414853-Benzyloxy-4-fluoro-phenylamine

Product 1

HCID 692871753-(3-Benzyloxy-4-fluoro-phenylamino)-but-2-enoic acid ethyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 8078CyclohexaneSolvent

Procedure

92.7 g (0.43 mol) of 3-Benzyloxy-4-fluoro-phenylamine, 57 ml (0.45 mol) of ethyl acetoacetate and 0.81 g (4 mmol) of p-toluenesulfonic acid monohydrate in 370 ml of cyclohexane were heated at reflux for 3 h in the presence of a water separator funnel. The reaction mixture was cooled to RT, ACOEt (1 l) and saturated aqueous NaHCO3 solution (0.5 l) were added, the layers were separated and the organic layer once extracted with AcOEt (0.3 l). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give 140 g (100%) of the desired 3-(3-benzyloxy-4-fluoro-phenylamino)-but-2-enoic acid ethyl ester as yellow-orange crystalline solid. Melting point: 79° C.-80° C.

Workup

  1. customthe layers were separated
  2. extractionthe organic layer once extracted with AcOEt (0.3 l)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5083ca4956e34c2cac1f041ff4076a48
Source dataset
uspto-grants-2004_11
Patent number
US06818767B2

Reaction notes

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