Sodium Carbonate → Methyl 2-[4-[4-(5-bromopyridin-2-yl)phenyl]cyclohexyl]acetate

HRID 1404246Notes

Reaction equation

HRID 1404246 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14](B3OC(C)(C)C(C)(C)O3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.Br[C:28]1[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][N:29]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(O)C>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH:5]1[CH2:6][CH2:7][CH:8]([C:11]2[CH:12]=[CH:13][C:14]([C:28]3[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][N:29]=3)=[CH:15][CH:16]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 693532,5-DibromopyridineHCID 57992171Methyl 2-(trans-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclohexyl)acetate

Product 1

HCID 66615782Methyl 2-[4-[4-(5-bromopyridin-2-yl)phenyl]cyclohexyl]acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of {4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester (4.0 g, 11.2 mmol, 1.0 equiv) and 2,5-dibromopyridine (3.2 g, 13.4 mmol, 1.2 equiv) in 50 Ml toluene/ethanol (1:1) was added 2 M Na2CO3 (16.8 Ml, 3 equiv) followed by Pd(PPh3)4 (0.38 g, 0.34 mmol, 0.03 equiv). The biphasic mixture was sparged with nitrogen for 10 min, then heated to 60° C. for 3 days. The reaction was cooled to room temperature and then partitioned between ethyl acetate and saturated ammonium chloride solution. The organic extracts were washed with brine, then dried over sodium sulphate and concentrated in vacuo. Purification by silica gel chromatography (7-40% EtOAc in hexanes) afforded the title compound as a yellow solid: 1H NMR (400 MHz, CDCl3) 1.11 (dd, J=13.01, 2.15 Hz, 2 H) 1.41-1.54 (m, 2 H) 1.76-1.90 (m, 5 H) 2.20 (d, J=6.57 Hz, 2 H) 2.46 (tt, J=12.09, 3.19 Hz, 1 H) 3.62 (s, 3 H) 7.23 (d, J=8.08 Hz, 2 H) 7.53 (dd, J=8.59, 0.76 Hz, 1 H) 7.77 (dd, J=8.46, 2.40 Hz, 1 H) 7.81 (q, J=3.87 Hz, 1 H) 7.81 (d, J=8.34 Hz, 1 H) 8.64 (d, J=1.77 Hz, 1 H); (M+H)+ 390.0.

Workup

  1. customThe biphasic mixture was sparged with nitrogen for 10 min
  2. temperatureThe reaction was cooled to room temperature
  3. custompartitioned between ethyl acetate and saturated ammonium chloride solution
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel chromatography (7-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e8ff22d850a24dc48f508cfd236dda09
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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