Water → (S)-Methyl 5-diazo-6-(methoxy(methyl)amino)-4,6-dioxo-3-(tritylamino)hexanoate

HRID 1844377Notes

Reaction equation

HRID 1844377 reaction equation
[CH3:1][O:2][N:3]([CH3:35])[C:4](=[O:34])[CH2:5][C:6](=[O:33])[C@@H:7]([NH:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:8][C:9]([O:11][CH3:12])=[O:10].O.CS([N:41]=[N+:42]=[N-])(=O)=O.N12CCCN=C1CCCCC2>C(#N)C.C(OCC)C>[N+:41](=[C:5]([C:4]([N:3]([O:2][CH3:1])[CH3:35])=[O:34])[C:6](=[O:33])[C@@H:7]([NH:13][C:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:8][C:9]([O:11][CH3:12])=[O:10])=[N-:42]

Participants

7

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 556271Methanesulfonyl azideHCID 46932672HCID 46932672, compound

Product 1

HCID 131732420(S)-Methyl 5-diazo-6-(methoxy(methyl)amino)-4,6-dioxo-3-(tritylamino)hexanoateYield 94%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

β-ketoamide 13 (3.70 g, 7.80 mmol, 1.0 equiv) was dissolved in 20.0 mL of acetonitrile (0.37 M) and H2O (0.14 mL, 1.0 equiv). Diazo transfer reagent, MeSO2N3 (1.02 mL, 11.70mmol, 1.5 equiv) and 1,8-Diazabicyclo[5.4.0]undec-7-ene (1.75 mL, 11.70 mmol, 1.5 equiv) were sequentially added. The resulting reaction mixture was permitted to stir for 4 h and then this reaction mixture was diluted with diethyl ether. The organic phase was washed sequentially with 10% NaOH, water, and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and then concentrated in vacuo. The oil was diluted in 1/1 ethyl acetate/hexanes and loaded onto a small plug of silica. The plug was eluted with 1/1 ethyl acetate/hexanes and the organics concentrated to provide the pure product 14 as a pale yellow foam (3.67 g) representing a 94% yield. X-ray quality crystals were grown from EtOAc/hexanes. m.p.=130-131° C.; [α]D27=−68.4° (c=4.3, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.47-7.49 (m, 6H); 7.19-7.22 (m, 6H), 7.13 (tt, J=1.6, 7.3 Hz, 3H), 4.88 (dt, J=5.7, 11.1 Hz, 1H), 3.68 (s, 3H); 3.60 (s, 3H); 3.11 (s, 3H), 2.74 (dd, J=6.1, 13.8 Hz, 1H); 2.61 (dd, J=6.1, 13.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 193.74, 161.01, 145.24, 128.04, 126.72, 125.31, 70.06, 60.18, 55.19, 50.77, 39.07, 32.65; IR (thin film): 3057, 2948, 2118, 1736, 1638, 1596, 1490, 1461, 1447, 1373, 1267, 1192, 1162, 1113, 1028, 940, 904, 776, 736, 706, 644 cm−1; HRMS [M+Na] for C28H28N4O5Na, calcd., 523.19519, found, 523.19997 (Error=9.1333 ppm).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic phase was washed sequentially with 10% NaOH, water, and brine
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe oil was diluted in 1/1 ethyl acetate/hexanes
  7. washThe plug was eluted with 1/1 ethyl acetate/hexanes
  8. concentrationthe organics concentrated

Sources & evidence

ORD record
ord-e8a183f703344a13b88e19b8473e6a87
Source dataset
uspto-grants-2015_02
Patent number
US08946408B2

Reaction notes

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