Diisopropylethylamine → (4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acid

HRID 1603999Notes

Reaction equation

HRID 1603999 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:23]([NH:26][C@@H:27]1[C@H:32]([O:33][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:31]=[C:30]([C:51]([O:53]C)=[O:52])[O:29][C@H:28]1[C:55]([O-:57])=O)(=[O:25])[CH3:24].C(N(CC)C(C)C)(C)C.[CH2:67]([CH2:75][CH2:76][CH2:77][NH2:78])[CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>CN(C)C=O>[C:23]([NH:26][C@H:27]1[C@H:28]([C:55](=[O:57])[NH:78][CH2:77][CH2:76][CH2:75][CH2:67][CH2:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[O:29][C:30]([C:51]([OH:53])=[O:52])=[CH:31][C@H:32]1[OH:33])(=[O:25])[CH3:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 140275BenzenepentanamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 86754843(2R,3S,4R)-3-acetylamino-4-(tert-butyldiphenylsilanyloxy)-3,4-dihydro-2H-pyran-2,6-dicarboxylic acid, 6-methyl ester

Product 1

HCID 70196688(4R,5R,6R)-5-Acetylamino-4-hydroxy-6-(phenethylpropylcarbamoyl)-5,6-dihydro-4H-pyran-2-carboxylic acidYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (1.42 g) was added to a solution of (2R,3S,4R)-3-acetylamino-4-(tert-butyldiphenylsilanyloxy)-3,4-dihydro-2H-pyran-2,6-dicarboxylic acid, 6-methyl ester (2 g) and N,N-diisopropylethylamine (1.4 ml) in dimethylformamide (5 ml), under nitrogen. To this was added N-phenethylpropylamine (722 mg) and the reaction was stirred at 23° C. for 16 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The organic extracts were dried over anhydrous sodium sulphate and the solvent was removed in vacuo to give a fawn foam. The foam was chromatographed over silica (Merck 9385, 45 g) using medium pressure (ca 4 psi) and ethyl acetate/cyclohexane (1:2 v/v) as the eluant. The required fractions were combined and the solvent removed in vacuo to give the title compound as a white foam (1.1 g). 1H NMR (250 MHz, CDCl3, rotamers) 7.6--7.1 (15H, m), 6.0+5.95 (1H, 2×m), 5.9--5.8 (1H, 2×d, J=6Hz), 5.2 (1H, 2×d, J=5Hz), 4.6 (1H, 2×d, J=3Hz), 4.0--3.7 (1H, m), 3.8 (3H, 2×s), 3.5--2.9 (4H, m), 2.8+2.5 (2H, 2×m), 2.0 (3H, 2×s), 1.5 --1.2 (2H, m), 1.1 (9H, s), 0.9+0.7 (3H, 2×t, J=7Hz).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between water and ethyl acetate
  3. dry with materialThe organic extracts were dried over anhydrous sodium sulphate
  4. customthe solvent was removed in vacuo
  5. customto give a fawn foam
  6. customThe foam was chromatographed over silica (Merck 9385, 45 g)
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-d11be401374e46b4a1f14f70b22c542c
Source dataset
uspto-grants-1999_11
Patent number
US05990156

Reaction notes

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