Potassium Carbonate → ethyl 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)(hydroxy)methyl)phenyl)acetate

HRID 1508998Notes

Reaction equation

HRID 1508998 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH:17]=[O:18])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:19](=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][C:40]([O:42][CH3:43])=[O:41])=[CH:35][CH:34]=2)O1>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C3C(=CC=CC=3)C=CC=2)C2C3C(=CC=CC=3)C=CC=2)C2C(=CC=CC=2)C=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH:17]([OH:18])[C:33]3[CH:34]=[CH:35][C:36]([CH2:39][C:40]([O:42][CH2:43][CH3:19])=[O:41])=[CH:37][CH:38]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 11219601Methyl 2-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetateHCID 903385542-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-4-carbaldehyde

Product 1

HCID 90112071ethyl 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)(hydroxy)methyl)phenyl)acetateYield 75%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 271443Tri(naphthalen-1-yl)phosphaneCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-4-carbaldehyde (0.210 g, 0.81 mmol) in dioxane (10 mL) was added palladium chloride (0.007 g, 0.040 mmol), trinaphthyl phosphine (0.017 g, 0.040 mmol), potassium carbonate 0.336 g, 2.43 mmol), and methyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (0.200 g, 0.97 mmol). The mixture was purged with nitrogen and then heated to 100° C. under sealed conditions for 16 h. After this time, the mixture was diluted with water and extracted with ethyl acetate. The organic layer were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.250 g, 75%) as a white foam. MW=421.9. 1H NMR (CDCl3, 500 MHz) δ 8.01-7.97 (m, 1H), 7.87-7.83 (m, 1H), 7.76 (s, 1H), 7.40-7.23 (m, 6H), 5.81 (s, 1H), 4.13 (q, J=7.0 Hz, 2H), 3.59 (s, 2H), 3.07-2.98 (m, 2H), 2.87-2.79 (m, 1H), 2.64-2.49 (m, 1H), 2.08 (quin, J=7.5 Hz, 2H), 1.30-1.21 (m, 3H); APCI MS m/z 422 [M+H]+.

Workup

  1. customThe mixture was purged with nitrogen
  2. additionAfter this time, the mixture was diluted with water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-ea6286a546b34db89b1df17cb219fe54
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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