4-Cyanophenylboronic acid → HCID 58993665, compound

HRID 391466Notes

Reaction equation

HRID 391466 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:27]=[C:28]([C:30](=[O:34])[N:31]([CH3:33])[CH3:32])[CH:29]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1.[C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)#[N:36]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:35]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:3]=[C:4]([CH2:5][O:6][CH2:7][C:8]3([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]3)[CH:27]=[C:28]([C:30]([N:31]([CH3:32])[CH3:33])=[O:34])[CH:29]=2)=[CH:39][CH:38]=1)#[N:36]

Participants

5

Reactant 2

HCID 27343264-Cyanophenylboronic acidHCID 58993667HCID 58993667, compound

Product 1

HCID 58993665HCID 58993665, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

tert-Butyl 4-((3-bromo-5-(dimethylcarbamoyl)benzyloxy)methyl)-4-phenylpiperidine-1-carboxylate (41.2 mg, 0.08 mmol), 4-cyanophenylboronic acid (34.3 mg, 0.23 mmol), and tetrakis(triphenylphosphine) palladium(0) (12.1 mg, 0.01 mmol) were combined in dry tetrahydrofuran (3 mL) in a microwave tube and sealed. After flushing with nitrogen, 0.28 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol and concentrated to afford 29 mg (66%). 1H-NMR (CD3OD, 500 MHz) δ 7.81-7.84 (m, 2H), 7.76 (s, 1H), 7.74 (s, 1H), 7.59 (s, 1H), 7.49 (s, 1H), 7.42-7.44 (m, 2H), 7.32-7.35 (m, 2H), 7.17-7.22 (m, 2H), 4.51 (s, 2H), 3.52 (s, 2H), 3.15 (s, 3H), 2.99 (s, 3H), 2.88-2.95 (m, 2H), 2.67-2.72 (m, 2H), 2.24-2.27 (m, 2H), 1.91-1.97 (m, 2H). 13C-NMR (CD3OD, 126 MHz) δ 172.2, 144.9, 144.2, 140.9, 139.9, 137.3, 132.9, 128.4, 128.1, 127.4, 127.2, 126.2, 125.7, 124.7, 118.7, 111.5, 79.9, 72.2, 42.1, 41.8, 39.1, 34.7, 32.7. Mass spec.: 454.31 (MH)+. Accurate mass spec.: m/z 454.2496 [MH]+, Δ=0.3 ppm.

Workup

  1. customsealed
  2. customAfter flushing with nitrogen, 0.28 mL of a 1 N potassium hydroxide aqueous solution
  3. additionwas introduced
  4. temperatureAfter cooling to room temperature
  5. concentrationthe reaction mixture was concentrated
  6. additiontreated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 1 h
  7. customThe solvent was removed in vacuo
  8. washAfter washing the column with several volumes of methanol
  9. washthe product was eluted
  10. washby washing the column with 2 M ammonia in methanol
  11. concentrationconcentrated
  12. customto afford 29 mg (66%)

Sources & evidence

ORD record
ord-4af8d99efbf841ecac292af5964144e4
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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