p-Toluenesulfonic acid monohydrate → HCID 178497267、化合物

HRID 480939

反応式

HRID 480939 の反応式
[CH:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=[CH:6]2)=O.[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[C@:25]([OH:40])([C@H:32]([S:34][CH:35]([CH2:38][OH:39])[CH2:36][OH:37])[CH3:33])[CH2:26][N:27]1[CH:31]=[N:30][CH:29]=[N:28]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[C@@:25]([OH:40])([CH2:26][N:27]1[CH:31]=[N:30][CH:29]=[N:28]1)[C@H:32]([S:34][C@@H:35]1[CH2:36][O:37][C@@H:1]([C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][CH:12]=2)[CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=[CH:6]3)[O:39][CH2:38]1)[CH3:33]

参加物

5

反応物 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 10594623(2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]-thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanolHCID 11521354Methyl 6-formyl-2-naphthalenecarboxylate

生成物 1

HCID 178497267HCID 178497267、化合物収率 56.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of methyl 6-formyl-2-naphthalenecarboxylate (227 mg, 1.06 mmol) obtained in example 3 (2), (2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanol (381 mg, 1.06 mmol) and p-toluenesulfonic acid monohydrate (363 mg, 1.91 mmol) in anhydrous tetrahydrofuran (50 ml) was concentrated at room temperature using a rotary evaporator under reduced pressure and then using a vacuum pump. A solution of the residue in anhydrous tetrahydrofuran (40 ml) was concentrated according to the procedure described above. The same procedure was repeated twice. A solution of the resulting residue in tetrahydrofuran (50 ml) was poured into a saturated aqueous sodium hydrogencarbonate solution cooled to 0° C. with stirring. The mixture was extracted with ethyl acetate and the organic layer was washed with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The oily residue was chromatographed on a silica gel column using ethyl acetate-hexane (1:2) as the eluant to afford methyl 6-[trans-5-[((1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-2-naphthalenecarboxylate (trans isomer, 331 mg, yield 56%) as a white solid, and then using ethyl acetate-hexane (3:1) as the eluant to afford methyl 6-[cis-5-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-2-naphthalenecarboxylate (cis isomer, 77 mg, yield 14%) as a colorless oil. The trans isomer was recrystallized from ethyl acetate-hexane to give white fluffy crystals.

後処理

  1. customa rotary evaporator under reduced pressure
  2. concentrationA solution of the residue in anhydrous tetrahydrofuran (40 ml) was concentrated
  3. additionA solution of the resulting residue in tetrahydrofuran (50 ml) was poured into a saturated aqueous sodium hydrogencarbonate solution
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic layer was washed with aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe oily residue was chromatographed on a silica gel column

出典と根拠

ORDレコード
ord-a936956fd81f42dfa9f5812bf2b6262e
出典データセット
uspto-grants-2003_11
特許番号
US06653330B2

関連ノート

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