Triphenyl phosphite → 10-Oxo-1,3,4,9,10,10a-hexahydro-2,4-a,5,9-tetraaza-phenanthrene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl ester

HRID 69673

Reaction equation

HRID 69673 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:18]1[C:27]([N+:28]([O-])=O)=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1.C([O-])([O-])=O.[K+].[K+].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1.[H][H]>C1COCC1.C(Cl)Cl.N.O[V](=O)=O.[Pt]>[CH3:25][O:24][C:22]([C:21]1[CH:26]=[C:27]2[C:18]([N:11]3[CH:10]([C:14](=[O:16])[NH:28]2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]3)=[N:19][CH:20]=1)=[O:23]

Participants

10

Reactant 5

HCID 7540Triphenyl phosphiteHCID 11430Potassium CarbonateHCID 346961Methyl 6-chloro-5-nitronicotinateHCID 51758554-[(Tert-butoxy)carbonyl]piperazine-2-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 5832446410-Oxo-1,3,4,9,10,10a-hexahydro-2,4-a,5,9-tetraaza-phenanthrene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl ester

Reagents, catalysts & solvents 4

HCID 23939PlatinumCatalystHCID 62684Ammonium metavanadate [UN2859] [Poison]CatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1169 mg, 5.08 mmol) in THF (46 mL) was added methyl 6-chloro-5-nitronicotinate (1000 mg, 4.62 mmol) and K2CO3 (638 mg, 4.62 mmol). The suspension was heated to reflux for 2 hours, cooled to room temperature, and filtered through a pad of celite. The celite was washed with DCM (50 mL) and the organic portions were combined. The solution was charged into a bomb hydroginator, then treated with triphenyl phosphite (0.015 ml, 0.048 mmol), ammonium vanadate (44 mg, 0.380 mmol), and platinum (1.853 g, 0.475 mmol). The reaction was sealed and pressurized with hydrogen gas (150 psi) overnight. The reaction was then diluted with DCM (100 mL) and heated to reflux for 1 hr. The hot mixture was filtered through celite, washed with DCM (50 mL), and concentrated to 1.65 g (96%) of the title compound as an off-white solid. [M+H] calc'd for C17H22N4O5, 363; found, 363.

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 2 hours
  3. filtrationfiltered through a pad of celite
  4. washThe celite was washed with DCM (50 mL)
  5. additionThe solution was charged into a bomb hydroginator
  6. customThe reaction was sealed
  7. temperatureheated
  8. temperatureto reflux for 1 hr
  9. filtrationThe hot mixture was filtered through celite
  10. washwashed with DCM (50 mL)
  11. concentrationconcentrated to 1.65 g (96%) of the title compound as an off-white solid

Sources & evidence

ORD record
ord-6bde964455ed47ac8d17197c36cadb6a
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Linked notes

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