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

HRID 1058406Notes

Reaction equation

HRID 1058406 reaction equation
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]

Participants

7

Reactant 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×HCID 226613232-Bromo-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-a8f7be1ca5ed48258f37faaa4d1e3389
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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