Potassium Carbonate → tert-Butyl 4-(4-(((benzyloxy)carbonyl)amino)-3-ethylphenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2272427Notes

Reaction equation

HRID 2272427 reaction equation
C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]=2)O1.Br[C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[C:32]([CH2:47][CH3:48])[CH:31]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CN(C=O)C>[CH2:39]([O:38][C:37]([NH:36][C:33]1[CH:34]=[CH:35][C:30]([C:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:17][CH:16]=2)=[CH:31][C:32]=1[CH2:47][CH3:48])=[O:46])[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 71232504benzyl N-(4-bromo-2-ethylphenyl)carbamate

Product 1

HCID 71232505tert-Butyl 4-(4-(((benzyloxy)carbonyl)amino)-3-ethylphenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 57.2%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (215 mg, 1.55 mmol) the tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (I37) (160 mg, 0.517 mmol), benzyl (4-bromo-2-ethylphenyl)carbamate (I34) (182 mg, 0.543 mmol), PdCl2(dppf)-DCM solvate (22 mg, 5 mol %) and DMF (5 mL) were loaded into a Schlenk tube, and degassed with 3× vacuum/nitrogen cycles. The mixture was brought to 80° C. under nitrogen then after 18 hours cooled and poured into water (100 mL). DCM (75 mL) and brine (50 mL) were added, the aqueous phase was washed with further DCM (2×75 mL), and the combined DCM extracts washed with brine, dried and evaporated. Chromatography (40 g silica cartridge, 0-80% ethyl acetate/petroleum benzine 40-60° C.) gave the title compound (I39) (129 mg, 57% yield) as a colourless oil; 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.45-7.31 (m, 5H), 7.22 (dd, J=8.5, 2.1 Hz, 1H), 7.18 (d, J=2.1 Hz, 1H), 6.48 (s, 1H), 5.99 (s, 1H), 5.21 (s, 2H), 4.06 (d, J=2.5 Hz, 2H), 3.63 (t, J=5.7 Hz, 2H), 2.58 (q, J=7.6 Hz, 2H), 2.50 (s, 2H), 1.49 (s, 9H), 1.22 (t, J=7.6 Hz, 3H). LCMS Method C: rt 6.67 min; m/z 337.1 [M-Boc+2H]+, 381.1 [M-tBu+2H]+.

Workup

  1. customdegassed with 3× vacuum/nitrogen cycles
  2. customwas brought to 80° C. under nitrogen
  3. temperatureafter 18 hours cooled
  4. additionpoured into water (100 mL)
  5. additionDCM (75 mL) and brine (50 mL) were added
  6. washthe aqueous phase was washed with further DCM (2×75 mL)
  7. washthe combined DCM extracts washed with brine
  8. customdried
  9. customevaporated

Sources & evidence

ORD record
ord-9fd4f3f3f1f74030adc8c2ad54d14d97
Source dataset
uspto-grants-2015_09
Patent number
US09120761B2

Reaction notes

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