Barium hydroxide → Tert-butyl{3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-2-[2'-(3-methoxypropyl)-3,6'-dimethylbiphenyl-4-yl]propyl}carbamate

HRID 2194901Notes

Reaction equation

HRID 2194901 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][C:29]3[C:34]([Cl:35])=[CH:33][C:32]([CH3:36])=[CH:31][C:30]=3[Cl:37])=[CH:21][CH:20]=2)[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[C:4]([CH3:38])[CH:3]=1.[CH3:39][O:40][CH2:41][CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([CH3:50])[C:45]=1B(O)O.C(COC)OC.O.[OH-].[Ba+2].[OH-]>O.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.[Pd]>[C:13]([O:12][C:11](=[O:17])[NH:10][CH2:9][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([C:45]2[C:46]([CH3:50])=[CH:47][CH:48]=[CH:49][C:44]=2[CH2:43][CH2:42][CH2:41][O:40][CH3:39])=[CH:3][C:4]=1[CH3:38])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][C:29]2[C:30]([Cl:37])=[CH:31][C:32]([CH3:36])=[CH:33][C:34]=2[Cl:35])=[CH:21][CH:20]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 6093286Barium hydroxideHCID 18180031Water 1,2-dimethoxyethaneHCID 58083342[2-(3-Methoxypropyl)-6-methylphenyl]boronic acidHCID 86658849Tert-butyl (2-(4-bromo-2-methylphenyl)-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}propyl)carbamate

Product 1

HCID 131730111Tert-butyl{3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-2-[2'-(3-methoxypropyl)-3,6'-dimethylbiphenyl-4-yl]propyl}carbamate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

To a solution tert-butyl (2-(4-bromo-2-methylphenyl)-3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}propyl)carbamate from EXAMPLE 2, step 2 (1 eq.) and [2-(3-methoxypropyl)-6-methylphenyl]boronic acid from step 1 (1.1 eq.) in 1-2 dimethoxyethane/water (6/1; 0.1M) at room temperature was added palladium tetrakis(triphenylphosphine) (0.05 eq.) and Barium hydroxide (1.5 eq.). The mixture was stiffed at 80° C. for 5 h, cooled to room temperature, poured in water and extracted with EtOAc. The organic extract was washed with, brine, dried over MgSO4 filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (10 to 70%, in 30 min) afforded the desired compound.

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed with, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography on silica gel (Combi-Flash by ISCO)
  8. washeluting with Hex/EtOAc (10 to 70%, in 30 min)

Sources & evidence

ORD record
ord-4d23e93d73854215a67c44ef0142da61
Source dataset
uspto-grants-2012_12
Patent number
US08334308B2

Reaction notes

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