Diisopropylethylamine → HCID 15480014, compound

HRID 1872223Notes

Reaction equation

HRID 1872223 reaction equation
C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([S:50]([N:53]([CH2:62][CH2:63][C:64]([O:66][CH3:67])=[O:65])[C:54]3([C:59]([OH:61])=O)[CH2:58][CH2:57][CH2:56][CH2:55]3)(=[O:52])=[O:51])=[CH:46][CH:45]=2)=[CH:40][CH:39]=1.Cl.[CH2:69]([O:76][NH2:77])[C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1>CN(C)C=O>[CH3:67][O:66][C:64](=[O:65])[CH2:63][CH2:62][N:53]([C:54]1([C:59](=[O:61])[NH:77][O:76][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[CH2:55][CH2:56][CH2:57][CH2:58]1)[S:50]([C:47]1[CH:48]=[CH:49][C:44]([C:41]2[CH:40]=[CH:39][C:38]([F:37])=[CH:43][CH:42]=2)=[CH:45][CH:46]=1)(=[O:51])=[O:52]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 102312Benzyloxyamine hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 15480013HCID 15480013, compound

Product 1

HCID 15480014HCID 15480014, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (4.3 mL, 24.6 mmole) and (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate (11.0 grams, 24.9 mmole) were added sequentially to a solution of 1-[(4'-fluorobiphenyl-4-sulfonyl)-(2-methoxycarbonylethyl)-amino]cyclopentane-1-carboxylic acid (10.1 grams, 22.4 mmole) in N,N-dimethylformamide (170 mL). The mixture was stirred for 4 hours. Additional diisopropylethylamine (7.8 mL, 44.6 mmole) and O-benzylhydroxylamine hydrochloride (4.64 grams, 29.1 mmole) were then added and the resulting mixture was stirred at 60° C. for 16 hours. After concentration under vacuum, the residue was taken up in water and acidified with 1 N aqueous hydrogen chloride solution. The mixture was extracted with ethyl acetate and the extract was washed sequentially with water, saturated aqueous sodium bicarbonate solution and brine. The solution was dried over magnesium sulfate and concentrated to give a solid which upon trituration with 7:3:1 hexane/ethyl acetate/methylene chloride provided 3-[(1-benzyloxycarbamoylcyclopentyl)-(4'-fluorobiphenyl-4-sulfonyl)amino]propionic acid methyl ester as a white crystalline solid (10.65 grams, 86%).

Workup

  1. stirringthe resulting mixture was stirred at 60° C. for 16 hours
  2. concentrationAfter concentration under vacuum
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe extract was washed sequentially with water, saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialThe solution was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a solid which upon trituration with 7:3:1 hexane/ethyl acetate/methylene chloride

Sources & evidence

ORD record
ord-8e3c0d2b997447f68f870a7289b55888
Source dataset
uspto-grants-2000_08
Patent number
US06107337

Reaction notes

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