Pyridinium, 1-(2-ethoxy-2-oxoethyl)-, bromide (1:1) → Methyl (4-(6-(1-((tert-butoxycarbonyl)amino)but-3-en-1-yl)-2-oxo-1,2-dihydropyridin-4-yl)-3-nitrophenyl)carbamate

HRID 1481278Notes

Reaction equation

HRID 1481278 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:28][CH:29]=[CH2:30])[C:10](=O)/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=1[N+:24]([O-:26])=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].C(O[C:35](=[O:43])[CH2:36][N+]1C=CC=CC=1)C.C([O-])(=O)C.[NH4+:48]>CCO>[C:1]([O:5][C:6]([NH:8][CH:9]([C:10]1[NH:48][C:35](=[O:43])[CH:36]=[C:12]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=2[N+:24]([O-:26])=[O:25])[CH:11]=1)[CH2:28][CH:29]=[CH2:30])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 87028Pyridinium, 1-(2-ethoxy-2-oxoethyl)-, bromide (1:1)HCID 517165Ammonium AcetateHCID 90060454Methyl (4-((1E,4S)-4-((tert-butoxycarbonyl)amino)-3-oxohepta-1,6-dien-1-yl)-3-nitrophenyl)carbamate

Product 1

HCID 122466939Methyl (4-(6-(1-((tert-butoxycarbonyl)amino)but-3-en-1-yl)-2-oxo-1,2-dihydropyridin-4-yl)-3-nitrophenyl)carbamateYield 67.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5F (3.0 g, 7.15 mmol) and 1-(2-ethoxy-2-oxoethyl)pyridinium bromide (1.189 g, 7.15 mmol) in EtOH (130 mL), was added ammonium acetate (11.03 g, 143 mmol) portion wise. After 15 min, the mixture was stirred at 75° C. The reaction mixture was then concentrated and dissolved in EtOAc. The organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine. The organic phase was dried over sodium sulfate, filtered and concentrated to yield a residue which was purified by normal phase chromatography to isolate 5G (2.2 g, 67%) as a brown solid. MS (ESI) m/z: 459.3 (M+H)+. The racemate was subjected to chiral separation using chiral AD-H 21×250 mm, eluting with a mixture of 35% (50/50 EtOH, i-PrOH and 0.1% DEA) and 65% CO2 with a flow rate of 70 mL/min and 150 bar at 40° C. to give enantiomer 5G1 (peak 1) and enantiomer 5G2 (peak 2).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutiondissolved in EtOAc
  3. washThe organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue which
  8. customwas purified by normal phase chromatography

Sources & evidence

ORD record
ord-b09c067aba7d4b78bfc24732104cbe8c
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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