Benzene → HCID 78324475, compound

HRID 2201947Notes

Reaction equation

HRID 2201947 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]([CH2:6][O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.Cl.[CH3:17][C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC=CC=1>O.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.CCO>[CH3:17][C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[CH:15]=[CH:14][C:5]([CH2:6][O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=2)=[CH:27][CH:26]=1

Participants

8

Reactant 4

HCID 241BenzeneHCID 10340Sodium CarbonateHCID 68728719HCID 68728719, compoundHCID 82828030HCID 82828030, compound

Product 1

HCID 78324475HCID 78324475, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

Ethyl 2-(4-bromobenzyloxy)acetate (304 mg, 1.113 mmol), (R)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)phenylboronic acid hydrochloride (300 mg, 1.113 mmol), tetrakis(triphenylphosphine)palladium(0) (64.3 mg, 0.056 mmol) and 2M Na2CO3 (aq.) (1113 μL, 2.226 mmol) were added to a vial with benzene (2 mL) and EtOH (0.6 mL). The reaction was heated under microwave irradiation at 100° C. for an hour and 120° C. for 0.5 h. The reaction was diluted with H2O (1 mL) and extracted with EtOAc (3×2 mL). The combined organics were filtered through a plug of MgSO4. The solvent was evaporated and the residue was purified by column chromatography and prep LCMS to give the title compound. LCMS m/z=382.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.26 (m, 3H), 1.39 (d, J=6.4 Hz, 3H), 1.54-1.70 (m, 1H), 1.85-2.12 (m, 2H), 2.15-2.29 (m, 1H), 2.96-3.14 (m, 2H), 3.14-3.28 (m, 2H), 3.40-3.49 (m, 1H), 3.54 (d, J=20.3 Hz, 1H), 3.59-3.70 (m, 1H), 4.09-4.21 (m, 4H), 4.59 (s, 2H), 7.36-7.49 (m, 4H), 7.66 (d, J=7.71 Hz, 4H), 9.51-10.13 (m, 1H).

Workup

  1. extractionextracted with EtOAc (3×2 mL)
  2. filtrationThe combined organics were filtered through a plug of MgSO4
  3. customThe solvent was evaporated
  4. customthe residue was purified by column chromatography and prep LCMS

Sources & evidence

ORD record
ord-1bbff44402f84392911d05eacc230d83
Source dataset
uspto-grants-2016_06
Patent number
US09365511B2

Reaction notes

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