Pyridine → HCID 21905286, compound

HRID 1247412Notes

Reaction equation

HRID 1247412 reaction equation
[C:1]([C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([OH:21])[C:14]=2[F:22])[O:11][CH3:12])=[CH:5][CH:4]=1)#[N:2].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:14]=2[F:22])[O:11][CH3:12])=[CH:24][CH:25]=1)#[N:2]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 66827Phenylboronic Acid2×HCID 21905115HCID 21905115, compound

Product 1

HCID 21905286HCID 21905286, compoundYield 58.4%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of (RS)-N-(4-cyano-benzyl)-2-(2-fluoro-3-hydroxy-4-methoxy-phenyl)-2-methoxy-acetamide (150 mg), phenyl boronic acid (58 mg), copper (II) acetate (79 mg), pyridine (0.18 ml) and activated molecular sieves (4 A) at rt in CH2Cl2 under an argon atmosphere was stirred for 24 h. More copper (II) acetate (40 mg), phenyl boronic acid (29 mg) and pyridine (0.9 ml) were added to the mixture and stirring was continued for 16 h. The mixture was filtered and the cake washed with 15 ml CH2Cl2. The filtrate was washed with 1.0 N HCl (25 ml), 1.0 N NaOH (25 ml) and brine (25 ml), dried (MgSO4), filtered and concentrated (rotavapor) to leave the crude product as a brown gum. The crude product was purified by flash chromatography (cyclohexane=5 cyclohexane/EtOAc 2:3) to give (RS)-N-(4-Cyano-benzyl)-2-(2-fluoro-4-methoxy-3-phenoxy-phenyl)-2-methoxy-acetamide (107 mg) as an off-white foam. MS 421.2 ([M+H]+)

Workup

  1. stirringstirring
  2. waitwas continued for 16 h
  3. filtrationThe mixture was filtered
  4. washthe cake washed with 15 ml CH2Cl2
  5. washThe filtrate was washed with 1.0 N HCl (25 ml), 1.0 N NaOH (25 ml) and brine (25 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated (rotavapor)
  9. customto leave the crude product as a brown gum
  10. customThe crude product was purified by flash chromatography (cyclohexane=5 cyclohexane/EtOAc 2:3)

Sources & evidence

ORD record
ord-ee7712876fba48afafbffd9525f83f4d
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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