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

HRID 483754Notizen

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Reaktionsgleichung von HRID 483754
[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]

Komponenten

11

Edukt 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

Produkt 1

HCID 67754048N-[(3S,4R)-3-Hydroxy-2,2-dimethyl-6-(trifluoromethoxy)-chroman-4-yl]-4,5-dimethoxy-2-nitrobenzamideAusbeute 56,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 241BenzeneLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 21927730Benzene methanolLösungsmittel

Versuchsvorschrift

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)-4amino-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° 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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5e6ffb004322492fbd1e01a51bbb65f6
Quelldatensatz
uspto-grants-1993_07
Patentnummer
US05225566

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