Hydrochloric Acid → 3-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzoic acid

HRID 1161067ノート

反応式

HRID 1161067 の反応式
[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16](O)[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].ClCCl.CN(S(F)(F)[F:38])C.Cl>[OH-].[Na+].O1CCCC1>[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([F:38])[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 123203Sulfur, trifluoro(N-methylmethanaminato)-2 回HCID 666995643-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid

生成物 1

HCID 578843923-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzoic acid収率 70%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
-78 °C

実験手順

A suspension of 3-{[4-(4-acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid (100 mg, 0.246 mmol) and dichloromethane (5 mL) is stirred at −78° C. Dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and the mixture is warmed to room temperature. An additional portion of dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and suspension becomes a solution. The reaction mixture is diluted with aqueous 2N sodium hydroxide (5 mL) and tetrahydrofuran (2 mL) and stirred 10 min. The pH is adjusted to 2 with aqueous 5N hydrochloric acid and extracted with ethyl acetate (2×20 mL). The combined extracts are concentrated and the resulting residue is purified via silica chromatography eluting with hexanes to 1:1 hexanes:ethyl acetate to give the title compound (70 mg, 70%) as a white solid. 1H NMR (DMSO-d6) δ 13.12 (s, 1H), 12.86 (s, 1H), 7.93-7.95 (m, 2H), 7.82 (d, 1H), 7.68 (d, 1H), 7.44-7.59 (m, 5H), 6.75-6.90 (d, 1H), 6.72 (d, 1H), 5.29 (s, 2H), 2.59 (s, 3H), 2.06 (s, 3H). LCMS M−1 407.

後処理

  1. temperaturethe mixture is warmed to room temperature
  2. stirringstirred 10 min
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. concentrationThe combined extracts are concentrated
  5. customthe resulting residue is purified via silica chromatography
  6. washeluting with hexanes to 1:1 hexanes

出典と根拠

ORDレコード
ord-f8d78276708b4052b83b7fb0006b078c
出典データセット
uspto-grants-2010_10
特許番号
US07816523B2

反応ノート

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