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

HRID 2096915ノート

反応式

HRID 2096915 の反応式
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]

参加物

7

反応物 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57539235HCID 57539235、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 9942167Palladium hydroxide触媒HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3e65c440228e406095c8626c649fb60b
出典データセット
uspto-grants-2013_05
特許番号
US08450336B2

反応ノート

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