Diisopropylethylamine → (2S,5R)-6-(allyloxy)-4-(methoxymethyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamide

HRID 627123Notes

Reaction equation

HRID 627123 reaction equation
[CH2:1]([O:4][NH:5][C@H:6]1[CH2:11][NH:10][C@H:9]([C:12]([NH2:14])=[O:13])[CH:8]=[C:7]1[CH2:15][O:16][CH3:17])[CH:2]=[CH2:3].C(N(C(C)C)C(C)C)C.Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>C(#N)C.CCOC(C)=O>[CH2:1]([O:4][N:5]1[C:28](=[O:30])[N:10]2[CH2:11][C@H:6]1[C:7]([CH2:15][O:16][CH3:17])=[CH:8][C@H:9]2[C:12]([NH2:14])=[O:13])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 89851857(2S,5R)-5-(allyloxyamino)-4-(methoxymethyl)-1,2,5,6-tetrahydropyridine-2-carboxamide2×

Product 1

HCID 89852257(2S,5R)-6-(allyloxy)-4-(methoxymethyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamideYield 84.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (2S,5R)-5-(allyloxyamino)-4-(methoxymethyl)-1,2,5,6-tetrahydropyridine-2-carboxamide (Intermediate 74, 1.12 g, 4.64 mmol) in acetonitrile (100 mL), N-ethyl-N-isopropylpropan-2-amine (4.04 mL, 3.00 g, 23.21 mmol) was added, then triphosgene (551 mg, 1.86 mmol) in 20 mL acetonitrile was added slowly via syringe pump over 4 h at 0° C. It was stirred from 0° C. to rt overnight. The solution was concentrated to give a residue, which was then taken up in 50 mL EtOAc and washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified on a silica gel column eluting with 0-100% ethyl acetate/hexanes gave a yellow oil (420 mg, 34%).

Workup

  1. concentrationThe solution was concentrated
  2. customto give a residue, which
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on a silica gel column
  8. washeluting with 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-59c5606fb50f4ce4ba23501a85459ac9
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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