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

HRID 1646328

反応式

HRID 1646328 の反応式
[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]

参加物

11

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 241Benzene溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 21927730Benzene methanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-dd879502e2b240eb8d59b22b22172a26
出典データセット
uspto-grants-1993_01
特許番号
US05179118

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