Potassium Carbonate → Methyl (4-((1E,4S)-4-((tert-butoxycarbonyl)amino)-3-oxohepta-1,6-dien-1-yl)-3-nitrophenyl)carbamate

HRID 1481277Notes

Reaction equation

HRID 1481277 reaction equation
COP([CH2:7][C:8](=[O:21])[C@@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:10][CH:11]=[CH2:12])(OC)=O.[CH:22]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:34])[O:32][CH3:33])=[CH:26][C:25]=1[N+:35]([O-:37])=[O:36])=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CCO>[C:16]([O:15][C:14]([NH:13][C@@H:9]([CH2:10][CH:11]=[CH2:12])[C:8](=[O:21])/[CH:7]=[CH:22]/[C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:34])[O:32][CH3:33])=[CH:26][C:25]=1[N+:35]([O-:37])=[O:36])=[O:20])([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 87132892(S)-tert-Butyl 1-(dimethoxyphosphoryl)-2-oxohex-5-en-3-ylcarbamateHCID 89410473Methyl (4-formyl-3-nitrophenyl)carbamate

Product 1

HCID 90060454Methyl (4-((1E,4S)-4-((tert-butoxycarbonyl)amino)-3-oxohepta-1,6-dien-1-yl)-3-nitrophenyl)carbamateYield 90%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a vigorously stirred solution of 5E (4.47 g, 13.92 mmol) and 5D (2.6 g, 11.60 mmol) in THF (anhydrous) (115 mL) and EtOH (absolute) (1.148 mL) under nitrogen was added portion wise K2CO3 (anhydrous) (2.56 g, 18.56 mmol) at 0° C. The reaction mixture was allowed to raise to rt and then the mixture was heated at 55° C. The reaction mixture was then filtered with the aid of EtOAc and the filtrate evaporated to a residue which was dissolved in a small amount of methylene chloride and purified by normal phase chromatography to give 5F (4.38 g, 90%) as yellow solid. MS (ESI) m/z: 420.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.22 (d, J=2.2 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.83-7.73 (m, 2H), 7.21 (d, J=7.7 Hz, 1H), 7.02 (d, J=15.9 Hz, 1H), 5.77 (ddt, J=17.0, 10.2, 6.7 Hz, 1H), 5.16-5.01 (m, 2H), 4.32 (td, J=8.5, 4.9 Hz, 1H), 3.71 (s, 3H), 2.34-2.23 (m, 1H), 1.36 (s, 9H) ppm.

Workup

  1. temperaturethe mixture was heated at 55° C
  2. filtrationThe reaction mixture was then filtered with the aid of EtOAc
  3. customthe filtrate evaporated to a residue which
  4. dissolutionwas dissolved in a small amount of methylene chloride
  5. custompurified by normal phase chromatography

Sources & evidence

ORD record
ord-491343d6ab5e4ea3b74d7f34779909e7
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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