Potassium Phosphate, Tribasic → Ethyl 5-(benzyloxy)-6-((tert-butoxycarbonyl)amino)nicotinate

HRID 509405Notes

Reaction equation

HRID 509405 reaction equation
[CH2:1]([O:8][C:9]1[C:10](Cl)=[N:11][CH:12]=[C:13]([CH:19]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:8][C:9]1[C:10]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[N:11][CH:12]=[C:13]([CH:19]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86687989Ethyl 5-(benzyloxy)-6-chloronicotinate

Product 1

HCID 71144248Ethyl 5-(benzyloxy)-6-((tert-butoxycarbonyl)amino)nicotinate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of ethyl 5-(benzyloxy)-6-chloronicotinate (2.1 g, 0.00719 mol) in THF (21 mL) in a 250 mL sealed tube, were added Pd2(dba)3 (395 mg, 0.00043 mol, Aldrich), NH2Boc (1.68 g, 0.0143 mol, Aldrich), X-phos (500 mg, 0.0010 mol, Aldrich) and K3PO4 (4.5 g, 0.0010 mol). The vessel was purged with argon gas for 10 min. The reaction mixture was then stirred for 12 h at 80° C. After completion of the reaction (monitored by TLC, 30% EtOAc in hexane), the reaction mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, and purified by column chromatography, silica gel (60-120 mesh) using 23-30% EtOAc in petroleum ether as the eluent to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 9.22 (s, 1H), 8.46 (d, J=1.8 Hz, 1H), 7.81 (d, J=1.8 Hz, 1H), 7.53 (d, J=6.6 Hz, 2H) 7.42-7.33 (m, 3H), 5.22 (s, 2H), 4.36 (q, J=6.9 Hz, 2H), 1.44 (s, 9H), 1.36 (t, 3H).

Workup

  1. customsealed tube
  2. customThe vessel was purged with argon gas for 10 min
  3. customAfter completion of the reaction (monitored by TLC, 30% EtOAc in hexane)
  4. customthe reaction mixture was quenched with water (50 mL)
  5. extractionextracted with EtOAc (50 mL×3)
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. custompurified by column chromatography, silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-cbfd72098a854e9281ad01dc0175b007
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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