Sodium Carbonate → Methyl (2-amino-4-chloro-5-fluorophenyl)acetate

HRID 374281ノート

反応式

HRID 374281 の反応式
[N+:1]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH3:15])=[O:13])([O-])=O.[PH2]([O-])=O.[Na+].N1C=CC=CC=1.[FH:26].F.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].[H][H].N1C=CC=CC=1.O>[NH2:1][C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([F:26])=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH3:15])=[O:13]

参加物

10

反応物 5

HCID 10340Sodium CarbonateHCID 14917Hydrofluoric Acid4 回HCID 64774Pyridine, hydrofluoride (1:1)2 回HCID 10944246Methyl 2-(4-chloro-2-nitrophenyl)acetateHCID 178527019HCID 178527019、化合物

生成物 1

HCID 10900080Methyl (2-amino-4-chloro-5-fluorophenyl)acetate

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 178418361HCID 178418361、化合物溶媒

実験手順

The starting compound (I) in Scheme 1 is readily prepared from methyl 2-(2-nitro-4-chlorophenyl)acetate, 5% palladium on carbon, sodium hypophosphite and water, pursuant to the reactions described by Johnstone, et al., Tetrahedron 34, 213, (1978). In step [a] compound (I) is reacted with either hydrogen fluoride-pyridine or anhydrous hydrogen fluoride. In the case of hydrogen fluoridepyridine, compound (I) is dissolved in a minimum amount of pyridine and added to an ice-bath cooled solution of the hydrogen fluoride-pyridine. After the addition, the temperature of the reaction is raised to 25° C. to 50° C. and the two reagents are allowed to react for one hour. The reaction mixture is cooled to room temperature and the pH of the mixture adjusted to 7 using a solution of weak base, preferably sodium carbonate. In the case of anhydrous hydrogen fluoride, compound (I) is cooled to -78° C. in a reaction vessel, anhydrous hydrogen fluoride is condensed into the reaction vessel and the vessel is sealed. The reaction mixture is warmed to 25° C. to 50° C. and stirred for between 3 to 4 hours. The reaction vessel is opened and excess hydrogen fluoride is aspirated off. In either case rearrangement occurs to produce methyl (2-amino-4-chloro-5-fluorophenyl)acetate (II). Compound (II) can be purified by standard techniques well known to those skilled in the art. Alternatively, compound (II) can be used directly for the next reaction step.

後処理

  1. additionadded to an ice-bath
  2. additionAfter the addition
  3. temperaturethe temperature of the reaction is raised to 25° C. to 50° C.
  4. customto react for one hour
  5. customcondensed into the reaction vessel
  6. customthe vessel is sealed
  7. temperatureThe reaction mixture is warmed to 25° C. to 50° C.

出典と根拠

ORDレコード
ord-eae2081489114c9292d9fd1def4b33f7
出典データセット
uspto-grants-1992_11
特許番号
US05166401

反応ノート

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