4-Methylmorpholine → 4-(benzyloxy)-3-tert-butyl-N-(2-oxo-2-((1R,2S,5R)-7-oxo-6-aza-bicyclo[3.2.1]octan-2-ylamino)ethyl)benzamide

HRID 2225268Notes

Reaction equation

HRID 2225268 reaction equation
[CH2:1]([O:8][C:9]1[CH:21]=[CH:20][C:12]([C:13]([NH:15][CH2:16][C:17](O)=[O:18])=[O:14])=[CH:11][C:10]=1[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:26][C@H:27]1[CH2:33][CH2:32][C@@H:31]2[CH2:34][C@H:28]1[C:29](=[O:42])[N:30]2C(OC(C)(C)C)=O.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CCOC(C)=O.CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:21]=[CH:20][C:12]([C:13]([NH:15][CH2:16][C:17](=[O:18])[NH:26][C@H:27]2[CH2:33][CH2:32][C@@H:31]3[CH2:34][C@H:28]2[C:29](=[O:42])[NH:30]3)=[O:14])=[CH:11][C:10]=1[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68767611(1R,2S,5R)-tert-butyl 2-amino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylateHCID 692860352-(4-(Benzyloxy)-3-tert-butylbenzamido)acetic acid

Product 1

HCID 692866964-(benzyloxy)-3-tert-butyl-N-(2-oxo-2-((1R,2S,5R)-7-oxo-6-aza-bicyclo[3.2.1]octan-2-ylamino)ethyl)benzamideYield 138.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(4-(benzyloxy)-3-tert-butylbenzamido)acetic acid (418 mg, 1.22 mmol) in anhyd DMF (8 mL) was added (1R,2S,5R)-tert-butyl 2-amino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate (287 mg, 1.11 mmol), BOP reagent (738 mg, 1.67 mmol), and N-methylmorpholine (366 μL, 3.34 mmol). The mixture was stirred at room temperature for 12 h under nitrogen atmosphere and then diluted with EtOAc (250 mL). The organic layer was washed with water (100 mL), 0.1 N HCl (100 mL), satd NaHCO3 (100 mL), and brine (50 mL), dried (Na2SO4), and concentrated in vacuo. 4-(benzyloxy)-3-tert-butyl-N-(2-oxo-2-((1R,2S,5R)-7-oxo-6-aza-bicyclo[3.2.1]octan-2-ylamino)ethyl)benzamide (713 mg, quant.) was isolated as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.81-6.93 (m, 8H), 6.69 (s, 1H), 5.15 (s. 1H); 5.16 (s, 1H), 4.13-4.06 (m, 4H), 3.20-2.80 (m, 2H), 2.40-1.30 (m, 6H), 1.52 (s, 9H), 1.42 (s, 9H); MS found: (M+H)+=564.

Workup

  1. washThe organic layer was washed with water (100 mL), 0.1 N HCl (100 mL), satd NaHCO3 (100 mL), and brine (50 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c0b37ab90cf14bbea34f93d1f3c77192
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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