Potassium Carbonate → tert-butyl 4-(2-(3-methoxy-3-oxopropyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 537353Notes

Reaction equation

HRID 537353 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11].B1([C:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH:24]=2)OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>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]>[CH3:13][O:12][C:10](=[O:11])[CH2:9][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH:24]=1

Participants

5

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 15712815Methyl 3-(2-bromophenyl)propanoate

Product 1

HCID 67111238tert-butyl 4-(2-(3-methoxy-3-oxopropyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
85 °C

Procedure

To Methyl 3-(2-bromophenyl)propanoate (715 mg, 2.94 mmol) and 3,6-dihydro-2H-pyridine-1-N-Boc-4-boronic acid pinacol ester (1.0 g, 3.23 mmol) were added to a flask, followed by Pd(dppf)Cl2 (151 mg, 0.21 mmol) and K2CO3 (1.22 g, 8.82 mmol). The reaction flask was purged with Ar (3×). Dry DMF (22 mL) was added and the solution was degassed for 10 min. The reaction mixture was heated to 85° C. overnight. The mixture was filtered through Celite and was concentrated. The crude residue was purified by silica gel chromatography (gradient, 10% to 30% EtOAc/hexanes) to give tert-butyl 4-(2-(3-methoxy-3-oxopropyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (23) as a pale yellow oil (970 mg, 96% yield). 1H NMR (400 MHz, CDCl3): δ 7.21-7.16 (m, 3H), 7.09-7.06 (m, 1H), 5.57-5.55 (m, 1H), 4.03 (q, 2H), 3.67 (s, 3H), 3.63 (t, 2H), 2.95-2.91 (m, 2H), 2.59-2.55 (m, 2H), 2.37-2.33 (m, 2H), 1.50 (s, 9H). LC/MS RT (5 min method)=2.10 min. Mass observed: 246.19 (M-Boc+H).

Workup

  1. customThe reaction flask was purged with Ar (3×)
  2. additionDry DMF (22 mL) was added
  3. customthe solution was degassed for 10 min
  4. filtrationThe mixture was filtered through Celite
  5. concentrationwas concentrated
  6. customThe crude residue was purified by silica gel chromatography (gradient, 10% to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-789bafd9bbd44ae1899c5bfb1ebe22ad
Source dataset
uspto-grants-2014_10
Patent number
US08859776B2

Reaction notes

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