Triethylamine → (R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-propionic acid methyl ester

HRID 885504Notes

Reaction equation

HRID 885504 reaction equation
[CH3:1][O:2][C:3](=[O:7])[C@H:4]([NH2:6])[CH3:5].[CH3:8][C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[C:13]([CH3:16])[C:14]=1[F:15].C(N(CC)CC)C>ClCCl.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH3:1][O:2][C:3](=[O:7])[C@H:4]([NH:6][C:11]1[CH:12]=[C:13]([CH3:16])[C:14]([F:15])=[C:9]([CH3:8])[CH:10]=1)[CH3:5]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 89020methyl D-alaninateHCID 17750045(4-Fluoro-3,5-dimethylphenyl)boronic acid

Product 1

HCID 69169830(R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-propionic acid methyl esterYield 38%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (R)-2-amino-propionic acid methyl ester (0.200 g, 1.940 mmol), 3,5-dimethyl-4-fluorophenylboronic acid (0.652 g, 3.880 mmol), Cu(OAc)2 (0.388 g, 2.134 mmol), and molecular sieves 4 Å (1.456 g) in 15 mL of dichloromethane, was added triethylamine (0.54 mL, 3.880 mmol). After stirring at room temperature under O2 for 39 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 chromatography (silica gel) eluting with 0-30% ethyl acetate/hexanes to give the title compound as brown oil (0.164 g, 38% yield). LC-MS: tR=8.1 min; m/z 226 (M+H)+.

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 chromatography (silica gel)
  5. washeluting with 0-30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-d7ae94593ca349cda855861dab4a39d1
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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