Phenol → Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl ester

HRID 911252ノート

反応式

HRID 911252 の反応式
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2].[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[Cu]Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 53432589tert-Butyl [(4-bromo-2-fluorophenyl)methyl]carbamate

生成物 1

HCID 66706560Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl ester収率 58%

試薬・触媒・溶媒 2

HCID 62652Cuprous chloride触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

Mix under argon atmosphere (4-bromo-2-fluorobenzyl)-carbamic acid tert-butyl ester (2.12 g, 7.0 mmol), phenol (1.32 g, 14 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (129 mg, 0.7 mmol), and cesium carbonate (4.56 g, 14 mmol) in anhydrous NMP (15 mL). Degas the flask, fill with argon and add copper(I) chloride (346 mg, 3.5 mmol) quickly. Degas the flask then fill with argon and heat at 120° C. for 5 h. Cool to ambient temperature, dilute with EtOAc and filter. Wash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine. Separate the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1) to obtain the desired intermediate (1.28 g, 58%). GC-MS m/z: 260 [M−C4H9)+].

後処理

  1. customDegas the flask
  2. customDegas the flask
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. filtrationfilter
  6. washWash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine
  7. customSeparate the organic layer
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate in vacuo
  10. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1)

出典と根拠

ORDレコード
ord-497ac4bede6f488f997b0335b454bf7d
出典データセット
uspto-grants-2011_09
特許番号
US08022062B2

反応ノート

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