Toluene → benzyl (4S,10aR)-1,5-dioxodecahydropyrido[1,2-a][1,4]diazepin-4-ylcarbamate

HRID 529493Notes

Reaction equation

HRID 529493 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C@H:10]([NH:23][C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[C:11]([N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@@H:14]1[C:19](OC)=[O:20])=[O:12].C[Al](C)C.C1(C)C=CC=CC=1>C(Cl)CCl>[O:20]=[C:19]1[NH:8][CH2:9][C@H:10]([NH:23][C:24](=[O:25])[O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:11](=[O:12])[N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]12

Participants

5

Reactant 3

HCID 1140TolueneHCID 16682925TrimethylaluminumHCID 86706206(R)-methyl 1-((S)-3-amino-2-(benzyloxycarbonylamino)propanoyl)piperidine-2-carboxylate trifluoroacetate

Product 1

HCID 86706208benzyl (4S,10aR)-1,5-dioxodecahydropyrido[1,2-a][1,4]diazepin-4-ylcarbamateYield 17%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (R)-methyl 1-((S)-3-amino-2-(benzyloxycarbonylamino)propanoyl)piperidine-2-carboxylate trifluoroacetate (601 mg, 1.26 mmol) in ClCH2CH2Cl (10 mL) at rt was added trimethylaluminum in toluene (1.89 mL, 3.78 mmol). The reaction was stirred in a sealed bottle at 75° C. for 3 days. After cooling to rt, the reaction was quenched with water and then aqueous 1 N HCl solution until the solution became clear. The aqueous solution was extracted with DCM (2×30 mL). The combined organic layers were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 50-100% EtOAc/Hex to give benzyl (4S,10aR)-1,5-dioxodecahydropyrido[1,2-a][1,4]diazepin-4-ylcarbamate (71 mg, 0.21 mmol, 17% yield) as a white solid. Anal. Calcd. for C17H21N3O4 m/z 331.4. found: 332.3 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.65-7.02 (m, 5H), 6.20 (d, J=5.5 Hz, 1H), 5.59 (s, 1H), 5.35-4.96 (m, 2H), 4.58 (s, 1H), 4.15 (d, J=13.3 Hz, 1H), 3.99-3.70 (m, 1H), 3.26-2.82 (m, 2H), 2.46-2.14 (m, 1H), 1.93-1.37 (m, 6H).

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction was quenched with water
  3. extractionThe aqueous solution was extracted with DCM (2×30 mL)
  4. washThe combined organic layers were washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified
  9. washeluting with a gradient of 50-100% EtOAc/Hex

Sources & evidence

ORD record
ord-c34d7ad50afa4b87b1ea90208f725843
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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