2-Benzyloxy-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]ethanol → (cis)-2-{4'-[4-((R)-2-Benzyloxy-1-hydroxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

HRID 1528988Notes

Reaction equation

HRID 1528988 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([C:12]1[C:13]([CH3:24])=[N:14][O:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([O:27][C:28]([C@@H:30]1[CH2:32][C@@H:31]1[C:33]1[CH:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][CH:34]=1)=[O:29])[CH3:26]>CCO>[CH2:25]([O:27][C:28]([C@@H:30]1[CH2:32][C@@H:31]1[C:33]1[CH:38]=[CH:37][C:36]([C:20]2[CH:21]=[CH:22][C:17]([C:16]3[O:15][N:14]=[C:13]([CH3:24])[C:12]=3[C@@H:10]([OH:11])[CH2:9][O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:18][CH:19]=2)=[CH:35][CH:34]=1)=[O:29])[CH3:26]

Participants

4

Reactant 2

HCID 665773582-Benzyloxy-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]ethanolHCID 66578588(cis)-2-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 66578269(cis)-2-{4'-[4-((R)-2-Benzyloxy-1-hydroxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Prepared according to the procedure described in Example 110, Step 3, using 2-benzyloxy-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]ethanol and (cis)-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester. After the reaction the crude material was dissolved in EtOH (3 mL) and purified via preparatory chiral HPLC (Chiralcel-AD column, 8% EtOH in hexanes, 70 minutes) to afford three separate compounds. The first compound off of the column, containing a mixture of cis-cyclopropyl diastereomers, was the title compound.

Workup

  1. customPrepared
  2. custompurified via preparatory chiral HPLC (Chiralcel-AD column, 8% EtOH in hexanes, 70 minutes)
  3. customto afford three
  4. customseparate compounds
  5. additionThe first compound off of the column, containing
  6. additiona mixture of cis-cyclopropyl diastereomers

Sources & evidence

ORD record
ord-7834b590238647ecb7c51c7cad7189fa
Source dataset
uspto-grants-2015_07
Patent number
US09090573B2

Reaction notes

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