Benzamide → N-[(3S,4R)-3-Hydroxy-2,2-dimethyl-6-(trifluoromethoxy)-chroman-4-yl]-4,5-dimethoxy-2-nitrobenzamide

HRID 1646328

반응식

HRID 1646328 반응식
[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[CH:11][C:6]([C:7]([O:9]C)=O)=[C:5]([N+:15]([O-:17])=[O:16])[CH:4]=1.[OH-].[K+].S(Cl)(Cl)=O.[NH2:24][C@@H:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][C:36]([F:39])([F:38])[F:37])[CH:33]=2)[O:28][C:27]([CH3:41])([CH3:40])[C@H:26]1[OH:42].C(N(CC)CC)C.C(N)(=O)C1C=CC=CC=1>O.C1C=CC=CC=1.ClCCl.CO.C1C=CC=CC=1>[OH:42][C@H:26]1[C@H:25]([NH:24][C:7](=[O:9])[C:6]2[CH:11]=[C:12]([O:13][CH3:14])[C:3]([O:2][CH3:1])=[CH:4][C:5]=2[N+:15]([O-:17])=[O:16])[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][C:36]([F:39])([F:37])[F:38])[CH:33]=2)[O:28][C:27]1([CH3:41])[CH3:40]

참가 물질

11

반응물 6

HCID 2331BenzamideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 117867Benzoic acid, 4,5-dimethoxy-2-nitro-, methyl esterHCID 15020328(3S,4R)-4-Amino-2,2-dimethyl-6-(trifluoromethoxy)-chroman-3-ol

생성물 1

HCID 67754048N-[(3S,4R)-3-Hydroxy-2,2-dimethyl-6-(trifluoromethoxy)-chroman-4-yl]-4,5-dimethoxy-2-nitrobenzamide수율 56.3%

시약·촉매·용매 4

HCID 241Benzene용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 21927730Benzene methanol용매

실험 절차

Methyl 4,5-dimethoxy-2-nitrobenzoate (4.8 g, 20 mmol) was hydrolyzed to the corresponding carboxylic acid by refluxing overnight with KOH (1.6 g, 40 mmol) in 1:1 methanol/benzene (100 mL). The mixture was concentrated to give the crude carboxylate, dissolved in H2O, and precipitated as 4,5-dimethoxy-2-nitrobenzoic acid with 2N HCl. This acid (2.27 g, 10 mmol) was then converted to the corresponding acid chloride by refluxing in benzene (30 mL) with thionyl chloride (1.66 g, 14 mmol) for 1 hour. The crude mixture was concentrated in vacuo and diluted with dichloromethane (10 mL). This solution was added to a cooled solution of (3S,4R)-4-amino-2,2-dimethyl-6-(trifluoromethoxy)-chroman-3-ol (2.75 g, 10 mmol), triethylamine (1.39 mL, 10 mmol) and dichloromethane (25 mL). The crude benzamide was worked-up in a method similar to that in Example 1 and chromatographed (1:1 hexanes/ethyl acetate) to afford 2.74 g (56%) of white solid: m.p. 97°-100°0 C.; 1H NMR (DMSO-d6): δ 9.00 (s, 1H), 7.62 (s, 1H), 7.39 (d, 1H), 7.25 (s, 1H), 7.16 (d, 1H), 6.86 (d, 1H), 5.86 (d, 1H), 4.96 (br t, 1H), 3.91 (s, 3H), 3.89 (s, 3H), 3.64 (dd, 1H), 1.43 (s, 3H), 1.20 (s, 3H).

후처리

  1. concentrationThe mixture was concentrated
  2. customto give the crude carboxylate
  3. customprecipitated as 4,5-dimethoxy-2-nitrobenzoic acid with 2N HCl
  4. concentrationThe crude mixture was concentrated in vacuo
  5. additiondiluted with dichloromethane (10 mL)
  6. customchromatographed (1:1 hexanes/ethyl acetate)

출처 및 근거

ORD 기록
ord-dd879502e2b240eb8d59b22b22172a26
출처 데이터셋
uspto-grants-1993_01
특허 번호
US05179118

연결된 노트

불러오는 중…