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

HRID 2406313노트

반응식

HRID 2406313 반응식
[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]

참가 물질

7

반응물 3

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

생성물 2

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 57417360Sodium chloride; water용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a75468e349ef425598185566ee38c42d
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809331B2

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