Pyridine → (1S,2S)-2-[4-((R)-7-Fluoro-4-phenoxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid

HRID 625712Notes

Reaction equation

HRID 625712 reaction equation
C([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])C.N1C=CC=CC=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[NH4+].[OH-]>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:25][C:23]1[CH:22]=[CH:21][C:20]([O:26][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:19]2[C:24]=1[C@H:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([C@H:7]3[CH2:8][C@@H:6]3[C:4]([OH:3])=[O:5])=[CH:10][CH:11]=1)[CH2:17][CH2:18]2

Participants

7

Reactant 4

HCID 1049PyridineHCID 14923Ammonium HydroxideHCID 66827Phenylboronic AcidHCID 118093712(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 118093716(1S,2S)-2-[4-((R)-7-Fluoro-4-phenoxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acidYield 23.5%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (Intermediate 5, 150 mg, 0.42 mmol), pyridine (dry; 0.133 mL, 1.68 mmol) and phenylboronic acid (308 mg, 2.53 mmol) are suspended in dichloromethane (10 mL), 4 Å molecular sieves and copper(II)acetate (153 mg, 1.52 mmol) are added and the mixture is stirred under oxygen atmosphere at room temperature for 20 h. NH4OH (2 M aqueous solution, 20 mL) is added and the mixture is extracted with dichloromethane. The organic phase is collected, dried over sodium sulfate and concentrated under vacuum. The crude product is purified by flash chromatography (10-100% ethyl acetate in cyclohexane) to give the title compound (Yield: 40 mg). LC (METHOD 9): tR=2.52 min; Mass spectrum (ES+): m/z=405 [M+H]+.

Workup

  1. extractionthe mixture is extracted with dichloromethane
  2. customThe organic phase is collected
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product is purified by flash chromatography (10-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-7a23061ba52b4d8cabed4ece24c33dde
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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