Trifluoroacetic acid → 2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid hydroxyamide

HRID 885503Notes

Reaction equation

HRID 885503 reaction equation
C([O:5][NH:6][C:7](=[O:23])[C@H:8]([NH:13][C:14]1[CH:19]=[C:18]([CH3:20])[C:17]([F:21])=[C:16]([CH3:22])[CH:15]=1)[CH2:9][CH2:10][CH2:11][CH3:12])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[OH:5][NH:6][C:7](=[O:23])[CH:8]([NH:13][C:14]1[CH:19]=[C:18]([CH3:20])[C:17]([F:21])=[C:16]([CH3:22])[CH:15]=1)[CH2:9][CH2:10][CH2:11][CH3:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86667068(R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid tert-butoxy-amide

Product 1

HCID 866670692-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid hydroxyamideYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-(4-fluoro-3,5-dimethyl-phenylamino)-hexanoic acid tert-butoxy-amide (0.737 g, 2.273 mmol) in 1 mL of dichloromethane, was added trifluoroacetic acid (9 mL). After stirring at room temperature for 87 h, the reaction mixture was concentrated under reduced pressure. The product was isolated by Flash chromatography (silica gel) eluting with 0-10% methanol/dichoromethane to give the title compound as a white solid (0.182 g, 30% yield). Pure analytical sample was obtained by RP-HPLC purification. LC-MS: tR=6.8 min; m/z 269 (M+H)+;)+; 1H NMR (500 MHz, CD3OD) δ 0.92 (t, J=7.05 Hz, 3H), 1.33-1.45 (m, 4H), 1.71-1.79 (m, 2H), 2.13 (d, J=2.02 Hz, 6H), 3.65 (t, J=7.05 Hz, 1H), 6.36 (d, J=5.88 Hz, 2H); 13C NMR (125.75 MHz, CD3OD) δ 14.24, 14.80, 23.50, 29.18, 33.99, 58.94, 115.65 (d, J=3.14 Hz), 125.69 (d, J=18.74 Hz), 143.30, 155.19 (d, J=233.14 Hz), 172.75; 19F NMR (470.58 MHz, CD3OD) δ −135.79.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customThe product was isolated by Flash chromatography (silica gel)
  3. washeluting with 0-10% methanol/dichoromethane

Sources & evidence

ORD record
ord-88e79117351645df95382155768dfdb5
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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