Potassium Carbonate → Toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester

HRID 902312

反応式

HRID 902312 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:22][CH2:21][C:20]3[C:15](=[C:16](Br)[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.Cl[Pd]Cl>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:16]1[CH:17]=[C:18]([F:23])[CH:19]=[C:20]2[C:15]=1[O:14][CH:13]([CH2:12][O:11][S:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)(=[O:9])=[O:10])[CH2:22][CH2:21]2

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 86609108(8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate

生成物 1

HCID 86609109Toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester収率 71.2%

試薬・触媒・溶媒 3

HCID 10876480Bis(tri-o-tolylphosphine)palladium(II) Dichloride触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of (8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (0.33 g, 0.795 mmol) and 2-chlorophenylboronic acid (249 mg, 1.589 mmol) in dioxane (9 mL) was added a solution of potassium carbonate (329 mg, 2.38 mmol) in water (3 mL) and the mixture purged with nitrogen for 20 minutes. Trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (31.2 mg, 0.0397 mmol) was added and the reaction mixture heated to reflux for 18 hours. The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL). The organic layer was separated, washed with water (100 mL) and saturated brine (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 253 mg (71%) of toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester as a colorless syrup. MS (ESI) m/z 464 ([M+NH4]+).

後処理

  1. customthe mixture purged with nitrogen for 20 minutes
  2. temperaturethe reaction mixture heated
  3. temperatureto reflux for 18 hours
  4. customThe cooled reaction mixture
  5. customwas then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL)
  6. customThe organic layer was separated
  7. washwashed with water (100 mL) and saturated brine (100 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto afford a yellow syrup
  12. customPurification by flash chromatography

出典と根拠

ORDレコード
ord-231dbad2696d49acb8cc0f1d4c9009eb
出典データセット
uspto-grants-2008_04
特許番号
US07365095B2

関連ノート

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