Benzoyl Peroxide → 4-(bromomethyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

HRID 508424노트

반응식

HRID 508424 반응식
[Cl:1][C:2]1[C:3]([CH3:16])=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8].[Br:17]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.P([O-])(OCC)OCC>ClCCCl.CCOC(C)=O.C(OCC)C>[Br:17][CH2:16][C:3]1[C:2]([Cl:1])=[CH:14][C:6]([C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8])=[C:5]([F:15])[CH:4]=1

참가 물질

9

반응물 5

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimide3회HCID 81531DiisopropylethylamineHCID 3780918DiethylphosphiteHCID 580423685-Chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamide

생성물 1

HCID 580423974-(bromomethyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide수율 43.9%

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of 5-chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamide (Preparation 14, 118 g, 0.45 mol) in 1,2-dichloroethane (1.25 L) was added N-bromosuccinimide (91 g, 0.51 mol) and benzoyl peroxide (5 g, 20 mmol) and the mixture heated to reflux for 18 hours. N-bromosuccinimide (30 g, 0.17 mol) was then added and the solution heated 24 hours more. A further portion of N-bromosuccinimide (20 g, 0.11 mol) was added and the solution heated for 3 hours, then cooled and washed with water (1 L) containing aqueous sodium thiosulphate solution (200 mL, 0.5 M). The organic layer was washed with water (500 mL), dried over sodium sulphate and concentrated in vacuo to yield a crude solid. To a solution of this crude solid in EtOAc (1 L) was added diisopropylethylamine (130 mL, 0.75 mol) and diethyl phosphite (27.6 g, 0.2 mol) and the mixture stirred for 5 hours under nitrogen, then washed with aqueous hydrochloric acid (1 L, 2 M), dried over magnesium sulphate and evaporated to yield a dark solid. Trituration with diethyl ether (200 mL) gave the first crop of title compound as a tan solid (68 g). The filtrate was purified by silica gel chromatography eluting with 10% EtOAc in DCM containing acetic acid (1%), followed by crystallization from acetonitrile (130 mL) to yield the second crop of the title compound (30 g).

후처리

  1. temperaturethe mixture heated
  2. temperatureto reflux for 18 hours
  3. temperaturethe solution heated 24 hours more
  4. temperaturethe solution heated for 3 hours
  5. temperaturecooled
  6. washwashed with water (1 L)
  7. additioncontaining aqueous sodium thiosulphate solution (200 mL, 0.5 M)
  8. washThe organic layer was washed with water (500 mL)
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated in vacuo
  11. customto yield a crude solid
  12. washwashed with aqueous hydrochloric acid (1 L, 2 M)
  13. dry with materialdried over magnesium sulphate
  14. customevaporated
  15. customto yield a dark solid

출처 및 근거

ORD 기록
ord-921a1883fa2b46ba92634ca2623bd51a
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096500B2

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