Triethylamine → (1S,2S)-2-{4-[(R)-4-(4-Benzyloxy-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester

HRID 625687Notes

Reaction equation

HRID 625687 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([OH:26])[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:38]4[CH:39]=[CH:40][C:35]([O:34][CH2:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[CH:36][CH:37]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27343144-Benzyloxy-phenylboronic acidHCID 118093712(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 118093741(1S,2S)-2-{4-[(R)-4-(4-Benzyloxy-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl esterYield 83%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (Intermediate 5, 0.6 g, 1.7 mmol), 4-benzyloxyphenylboronic acid (1.53 g, 6.7 mmol), copper (II) acetate (306 mg, 1.7 mmol), triethylamine (1.83 mL, 13.1 mmol), 4-dimethylaminopyridine (21 mg, 0.17 mmol) and 4 Å molecular sieves (3 g) are suspended in dichloromethane and stirred under an oxygen atmosphere over a weekend. The mixture is filtered through a plug of CELITE filter aid, washing the filter cake with dichloromethane. The organic phases are washed with 1 M aqueous HCl solution, dried and the solvent removed. The residue is purified by flash chromatography (0-40% ethyl acetate in cyclohexane) to give the title compound (Yield 0.76 g). LC (METHOD 6): tR=1.04 min; Mass spectrum (ES+): m/z=539 [M+H]+.

Workup

  1. filtrationThe mixture is filtered through a plug of CELITE
  2. filtrationfilter aid
  3. washwashing the filter cake with dichloromethane
  4. washThe organic phases are washed with 1 M aqueous HCl solution
  5. customdried
  6. customthe solvent removed
  7. customThe residue is purified by flash chromatography (0-40% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-18c54bf2e62141dea10540a63112fb33
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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