Triethylamine → N-[(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-4-nitro-benzenesulfonamide

HRID 538369ノート

反応式

HRID 538369 の反応式
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:21][S:22]([C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)(=[O:24])=[O:23])([CH3:20])[CH2:9][O:10][C@@:11]([CH3:19])([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:14])=O)[C:5]([F:34])=[CH:4][CH:3]=1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:21][S:22]([C:25]2[CH:26]=[CH:27][C:28]([N+:31]([O-:33])=[O:32])=[CH:29][CH:30]=2)(=[O:23])=[O:24])([CH3:20])[CH2:9][O:10][C@@:11]([C:12]#[N:14])([CH3:19])[C:15]([F:18])([F:17])[F:16])[C:5]([F:34])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 9845Trifluoroacetic anhydride2 回HCID 86668077(R)-2-[(R)-2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide

生成物 1

HCID 86668078N-[(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-4-nitro-benzenesulfonamide収率 99.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
2.5 °C

実験手順

A suspension of (R)-2-[(R)-2-(6-bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide (8.43 g, 14.70 mmol) and triethylamine (5.12 ml, 36.8 mmol) in 85 ml DCM was cooled to 0-5° C. Trifluoroacetic anhydride (2.49 ml, 17.64 mmol) was added dropwise over 30 min. Additional triethylamine (1.54 ml, 11.07 mmol) and trifluoroacetic anhydride (0.75 ml, 5.29 mmol) were added to complete the reaction. The reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water. The emulsion was stirred for 15 min, more water and DCM were added and the layers were separated. The organic layer was dried with MgSO4H2O, filtered and evaporated. Purification by column chromatography on a silica gel (hexanes/10-25% EtOAc) gave 8.09 g of the title compound as a yellow resin.

後処理

  1. customthe reaction
  2. customThe reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water
  3. additionmore water and DCM were added
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried with MgSO4H2O
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by column chromatography on a silica gel (hexanes/10-25% EtOAc)

出典と根拠

ORDレコード
ord-d985c6b6f50a49a0ba84fe870e56369c
出典データセット
uspto-grants-2014_10
特許番号
US08865712B2

反応ノート

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