Ethyl Acetate → Tert-butyl 4-amino-3-chloro-2-fluorobenzoate

HRID 2406313ノート

反応式

HRID 2406313 の反応式
[Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:23])[CH:11]=1.C(OCC)(=O)C>CN(C)C=O.[Cl-].[Na+].O>[NH2:9][C:10]1[C:22]([Cl:1])=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])=[C:12]([F:23])[CH:11]=1.[NH2:9][C:10]1[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])=[C:12]([F:23])[C:11]=1[Cl:1]

参加物

7

反応物 3

HCID 8857Ethyl AcetateHCID 31398ChlorosuccinimideHCID 10058989Tert-butyl 4-amino-2-fluorobenzoate

生成物 2

HCID 68684306Tert-butyl 4-amino-5-chloro-2-fluorobenzoate収率 23%HCID 86687946Tert-butyl 4-amino-3-chloro-2-fluorobenzoate収率 28%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of N-chlorosuccinimide (950 mg, 7.1 mmol) in N,N-dimethylformamide (25 mL) was added dropwise a solution of tert-butyl 4-amino-2-fluorobenzoate (1.5 g, 7.1 mmol) in N,N-dimethylformamide (22 mL). The resulting mixture was stirred at room temperature for 3 hours and then brine solution (80 mL) and ethyl acetate (100 mL) were added. The organic phase was collected and washed three times with brine (50 mL). Combined organic phases were dried on magnesium sulphate and evaporated under reduced pressure. Purification of the residue via silica gel column chromatography (4% EtOAc in iso-hexane) gave tert-butyl 4-amino-5-chloro-2-fluorobenzoate (400 mg, 23%, 1H NMR (400 MHz, DMSO-d6): δ 7.63 (d, J=7.6 Hz, 1H), 6.55 (d, J=13.2 Hz, 1H), 6.46 (brs, 2H), 1.52 (s, 9H)) and tert-butyl 4-amino-3-chloro-2-fluorobenzoate (490 mg, 28%, 1H NMR (400 MHz, DMSO-d6): δ 7.52 (t, J=8.4 Hz, 1H), 6.64 (dd, J=1.2 Hz and J=8.4 Hz, 1H), 6.50 (brs, 2H), 1.53 (s, 9H)) both as a white solid.

後処理

  1. customThe organic phase was collected
  2. washwashed three times with brine (50 mL)
  3. customCombined organic phases were dried on magnesium sulphate
  4. customevaporated under reduced pressure
  5. customPurification of the residue via silica gel column chromatography (4% EtOAc in iso-hexane)

出典と根拠

ORDレコード
ord-a75468e349ef425598185566ee38c42d
出典データセット
uspto-grants-2014_08
特許番号
US08809331B2

反応ノート

読み込み中…