Triethylamine → (R)-methyl 2-(4-fluoro-3,5-dimethylphenylamino)-6-(4-fluoro-3-methylbenzyloxy)hexanoate

HRID 885517Notes

Reaction equation

HRID 885517 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][C@@H:12]([NH2:17])[C:13]([O:15][CH3:16])=[O:14])=[CH:4][C:3]=1[CH3:20].[CH3:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[C:26]([CH3:29])[C:27]=1[F:28].C(N(CC)CC)C>ClCCl.CC([O-])=O.CC([O-])=O.[Cu+2]>[F:28][C:27]1[C:26]([CH3:29])=[CH:25][C:24]([NH:17][C@H:12]([CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C:5]2[CH:18]=[CH:19][C:2]([F:1])=[C:3]([CH3:20])[CH:4]=2)[C:13]([O:15][CH3:16])=[O:14])=[CH:23][C:22]=1[CH3:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 17750045(4-Fluoro-3,5-dimethylphenyl)boronic acidHCID 69170604(R)-methyl 6-(4-fluoro-3-methylbenzyloxy)-2-aminohexanoate

Product 1

HCID 69170379(R)-methyl 2-(4-fluoro-3,5-dimethylphenylamino)-6-(4-fluoro-3-methylbenzyloxy)hexanoateYield 68.6%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of crude (R)-methyl 6-(4-fluoro-3-methylbenzyloxy)-2-aminohexanoate (0.128 g, 0.453 mmol), 3,5-dimethyl-4-fluorophenylboronic acid (0.152 g, 0.906 mmol), Cu(OAc)2 (0.090 g, 0.498 mmol), and molecular sieves 4 Å (0.400 g) in 5 mL of dichloromethane, was added triethylamine (0.13 mL, 0.906 mmol). After stirring at room temperature under O2 (1 atm) for 44 h, the reaction mixture was filtered through a pad of Celite and washed with dichloromethane. The filtrate was concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-30% ethyl acetate/hexanes to give the title compound as light yellow oil (0.126 g, 68% yield). GC-MS: tR=7.0 min; m/z 405 (M+).

Workup

  1. filtrationthe reaction mixture was filtered through a pad of Celite
  2. washwashed with dichloromethane
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe product was isolated by Flash column chromatography (silica gel column)
  5. washeluting with 0-30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-aec8c467cd34484b990399b7b03507f3
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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