Acetic Anhydride → 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide

HRID 2096915노트

반응식

HRID 2096915 반응식
C([N:8](CC1C=CC=CC=1)[CH:9]([CH2:22][O:23][CH:24]([F:26])[F:25])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11])C1C=CC=CC=1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>C(O)C.ClCCl.[OH-].[OH-].[Pd+2]>[NH2:8][CH:9]([CH2:22][O:23][CH:24]([F:25])[F:26])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11]

참가 물질

7

반응물 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57539235HCID 57539235, 화합물

생성물 1

HCID 685361582-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide수율 69.2%

시약·촉매·용매 3

HCID 9942167Palladium hydroxide촉매HCID 702Ethanol용매HCID 6344Dichloromethane용매2회

실험 절차

2-dibenzylamino-N-(3,4-difluoro-benzyl)-3-difluoromethoxy-propionamide (298 mg, 0.645 mmol) was stirred with 10% Pd(OH)2 (200 mg) in ethanol under H2 overnight. The reaction mixture was filtered and concentrated. The residue was mixed with triethylamine (254 mg, 2.5 mmol) in dichloromethane (2 mL) and treated with acetic anhydride (85 μL) at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was concentrated with silica gel and purified by column chromatography, eluting with 30-100% ethyl acetate in hexanes. The product was triturated with diethyl ether to give 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide (125 mg, 60%) as a white solid, MP: 146° C. 1H NMR (300 MHz, CDCl3): δ(ppm) 6.92-7.16 (m, 4H), 6.47 (d, 1H), 6.25 (wt, 1H), 4.75 (m, 1H), 4.41 (m, 2H), 4.22 (dd, 1H), 4.02 (dd, 1H) and 2.05 (s, 3H).

후처리

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. washwashed with water
  4. concentrationThe organic layer was concentrated with silica gel
  5. custompurified by column chromatography
  6. washeluting with 30-100% ethyl acetate in hexanes
  7. customThe product was triturated with diethyl ether

출처 및 근거

ORD 기록
ord-3e65c440228e406095c8626c649fb60b
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450336B2

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