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

HRID 911252노트

반응식

HRID 911252 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 62652Cuprous chloride촉매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
120 °C

실험 절차

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)+].

후처리

  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)

출처 및 근거

ORD 기록
ord-497ac4bede6f488f997b0335b454bf7d
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022062B2

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