Tri-o-tolylphosphine → HCID 71143784, compound

HRID 2406614Notes

Reaction equation

HRID 2406614 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:26])([F:25])[C:9]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])([OH:16])[CH2:10][N:11]2[CH:15]=[N:14][N:13]=[N:12]2)=[N:6][CH:7]=1.[CH2:27]([N:30]1[CH:34]=[N:33][N:32]=[N:31]1)[CH:28]=[CH2:29].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)C>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:30]1([CH2:27]/[CH:28]=[CH:29]/[C:2]2[CH:3]=[CH:4][C:5]([C:8]([F:26])([F:25])[C:9]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])([OH:16])[CH2:10][N:11]3[CH:15]=[N:14][N:13]=[N:12]3)=[N:6][CH:7]=2)[CH:34]=[N:33][N:32]=[N:31]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 521913N,N-Diethyl-2-propanamineHCID 120481901H-Tetrazole, 1-(2-propenyl)-HCID 71142816HCID 71142816, compound

Product 1

HCID 71143784HCID 71143784, compoundYield 14.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of compound 1 (200 mg, 0.46 mmol) in DMF (2 mL) were added compound T (161 mg, 1.47 mmol), tri-o-tolylphosphine (447 mg, 0.14 mmol), Pd(OAc)2 (22.7 mg, 0.10 mmol) and N,N-diethylisopropylamine (DIEA; 179 mg, 1.38 mmol) at RT, and the mixture was purged with inert gas for 15 min. The resulting reaction mixture was stirred at 110° C. under microwave heating for 15 min; progress of the reaction was monitored by TLC. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography (eluting with 75% EtOAc/hexanes) afforded 42 (30 mg, 0.06 mmol, 14.3%). 1H NMR (500 MHz, CDCl3): δ 8.73 (s, 1H), 8.67 (s, 1H), 8.49 (s, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.37-7.31 (m, 2H), 6.78-6.68 (m, 1H), 6.67-6.64 (m, 1H), 6.61 (s, OH), 6.53-6.48 (m, 1H), 5.52 (d, J=14.5 Hz, 1H), 5.27 (d, J=6.0 Hz, 2H), 5.16 (d, J=14.5 Hz, 1H). MS (ESI): m/z 462 [M+H]+. HPLC: 94.2%.

Workup

  1. customthe mixture was purged with inert gas for 15 min
  2. customThe resulting reaction mixture
  3. temperatureheating for 15 min
  4. temperatureThe reaction mixture was cooled to RT
  5. extractionextracted with EtOAc (2×50 mL)
  6. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto obtain the crude material
  10. customPurification
  11. washby silica gel column chromatography (eluting with 75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-aab5930b1b2141b79538e84f6badf18b
Source dataset
uspto-grants-2014_08
Patent number
US08809378B2

Reaction notes

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