Diisopropylamine → 4'-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethoxy]-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide hydrochloride

HRID 2220435Notes

Reaction equation

HRID 2220435 reaction equation
[NH2:1][C@@H:2]([CH3:12])[C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[OH:4].C(NC(C)C)(C)C.Br[CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[O:37])=[C:32]([S:43][CH:44]([CH3:46])[CH3:45])[CH:31]=2)=[CH:26][CH:25]=1.O1CCOCC1.[ClH:53]>CN(C)C=O>[ClH:53].[OH:4][C@H:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[C@@H:2]([NH:1][CH2:21][CH2:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[O:37])=[C:32]([S:43][CH:44]([CH3:45])[CH3:46])[CH:31]=2)=[CH:28][CH:29]=1)[CH3:12]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 6931143P-HydroxynorephedrineHCID 204431481,4-Dioxane hydrochlorideHCID 691025354'-(2-bromoethoxy)-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide

Product 1

HCID 691033674'-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethoxy]-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[(1R,2S)-2-amino-1-hydroxypropyl]-phenol (96.6 mg) in N,N-dimethylformamide (1.00 ml) were added diisopropylamine (156 μl) and 4′-(2-bromoethoxy)-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide (210 mg) at room temperature and stirred at 100° C. for 5 hours. To the reaction mixture was added hydrogen chloride 1,4-dioxane solution (4M, 464 μl) and stirred at 0° C. The mixture was filtrated and the filtrate was concentrated in vacuo. The residue was washed with ethyl ether three times, dried and purified with reverse phase silica gel column chromatography. To the resulting solution was added hydrogen chloride ethyl acetate solution (4M, 111 μl) and concentrated in vacuo to give 4′-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethoxy]-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide hydrochloride (108 mg).

Workup

  1. stirringstirred at 0° C
  2. filtrationThe mixture was filtrated
  3. concentrationthe filtrate was concentrated in vacuo
  4. washThe residue was washed with ethyl ether three times
  5. customdried
  6. custompurified with reverse phase silica gel column chromatography
  7. additionTo the resulting solution was added hydrogen chloride ethyl acetate solution (4M, 111 μl)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb0ba98dc4da42bdbb1d0539054491c1
Source dataset
uspto-grants-2008_08
Patent number
US07417060B2

Reaction notes

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