Diisopropylethylamine → (2S,5R)-6-(benzyloxy)-3-(((tert-butyldimethylsilyl)oxy)methyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamide

HRID 627187Notes

Reaction equation

HRID 627187 reaction equation
[CH2:1]([O:8][NH:9][C@H:10]1[CH2:15][NH:14][CH:13]([C:16]([NH2:18])=[O:17])[C:12]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:8][N:9]1[C:38](=[O:40])[N:14]2[CH2:15][C@H:10]1[CH:11]=[C:12]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:22])[CH3:23])[C@H:13]2[C:16]([NH2:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429Triphosgene2×HCID 123580399(5R)-5-((benzyloxy)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,5,6-tetrahydropyridine-2-carboxamide2×

Product 1

HCID 89852172(2S,5R)-6-(benzyloxy)-3-(((tert-butyldimethylsilyl)oxy)methyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamideYield 110%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (5R)-5-((benzyloxy)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,5,6-tetrahydropyridine-2-carboxamide (Intermediate 163, 0.562 g, 1.44 mmol) and diisopropylethyl amine (1.000 mL, 5.74 mmol) in acetonitrile (200 mL) at 0° C. was added triphosgene (0.145 g, 0.49 mmol) as a solution in acetonitrile (6 mL). The triphosgene solution was added at a rate of 4 mL/hour. Once addition was complete the reaction was stirred at 0° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate. The aqueous layer was extracted again with EtOAc and then DCM. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0%-100, ethyl acetate/hexanes) afforded the title compound (0.225 g, 37.5%) as a colorless film.

Workup

  1. additionOnce addition
  2. washwashed with saturated sodium bicarbonate
  3. extractionThe aqueous layer was extracted again with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b0436d15329e42ec9a3e81fcc3d29bca
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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