1-Hydroxybenzotriazole → Rac.-n-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

HRID 1058406ノート

反応式

HRID 1058406 の反応式
C(N(C(C)C)CC)(C)C.[CH3:10][O:11][C:12](=[O:21])[CH:13]([P:15]([O:19][CH3:20])([O:17][CH3:18])=[O:16])[NH2:14].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.ON1C2C=CC=CC=2N=N1.[Br:56][C:57]1[CH:65]=[C:64]([C:66]([NH:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([OH:76])[CH:71]=2)=[O:67])[CH:63]=[CH:62][C:58]=1[C:59](O)=[O:60]>CN(C)C=O>[CH3:10][O:11][C:12](=[O:21])[CH:13]([P:15]([O:17][CH3:18])([O:19][CH3:20])=[O:16])[NH:14][C:59](=[O:60])[C:58]1[CH:62]=[CH:63][C:64]([C:66]([NH:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([OH:76])[CH:71]=2)=[O:67])=[CH:65][C:57]=1[Br:56]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11084793Methyl 2-amino-2-(dimethoxyphosphoryl)acetate2 回HCID 226613232-Bromo-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid

生成物 1

HCID 23560709Rac.-n-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester収率 76%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

Diisopropylethylamine (1.81 g, 14 mmol) was added to a solution of rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (5.00 g, 15.1 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (5.20 g, 13.7 mmol), 1-hydroxybenzotriazole (1.85 g, 13.7 mmol) and 2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid (Example 79; 4.80 g, 13.7 mmol) in N,N-dimethylformamide (50 mL). After the reaction was stirred for 4 h at 25° C., the volatiles were removed in vacuo. A solution of the residue in ethyl acetate (200 mL) was washed with 1N hydrochloric acid solution (100 mL), saturated aqueous sodium bicarbonate solution (100 mL), water (100 mL) and brine (100 mL). The organic layer was dried over MgSO4, filtered, concentrated and the resulting residue was flash chromatographed over silica gel (ethyl acetate-3% methanol in ethyl acetate) to give rac.-N-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (5.50 g, 76% yield) as a colorless foam.

後処理

  1. customthe volatiles were removed in vacuo
  2. washA solution of the residue in ethyl acetate (200 mL) was washed with 1N hydrochloric acid solution (100 mL), saturated aqueous sodium bicarbonate solution (100 mL), water (100 mL) and brine (100 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed over silica gel (ethyl acetate-3% methanol in ethyl acetate)

出典と根拠

ORDレコード
ord-a8f7be1ca5ed48258f37faaa4d1e3389
出典データセット
uspto-grants-2003_02
特許番号
US06515124B2

反応ノート

読み込み中…