Diisopropylethylamine → (s)-2-Hydroxy-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide

HRID 990395Notes

Reaction equation

HRID 990395 reaction equation
[CH3:1][CH:2]([CH2:4][C@H:5]([OH:9])[C:6]([OH:8])=O)[CH3:3].C(N(CC)C(C)C)(C)C.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[CH2:27][CH2:28][CH2:29][NH2:30])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:31]2[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=2)[CH2:27][CH2:28][CH2:29][NH:30][C:6](=[O:8])[C@@H:5]([OH:9])[CH2:4][CH:2]([CH3:1])[CH3:3])=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83697Leucic acid, L-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13530069HCID 13530069, compound

Product 1

HCID 53948997(s)-2-Hydroxy-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amideYield 48.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

L-2-hydroxyisocaproic acid (102 mg, 0.77 mmol) was dissolved in DMF (5 mL) and treated with N,N-diisopropylethylamine (0.53 mL, 3.06 mmol), 4,4-bis-(4-fluorophenyl)-butylamine (200 mg, 0.77 mmol), and HBTU (292 mg, 0.77 mmol), then stirred overnight at room temperature. The reaction was diluted with EtOAc (125 mL), washed with saturated bicarbonate solution and brine, dried over Na2SO4, and concentrated. The residue was chromatographed twice on silica gel, eluting with 2-4% MeOH/CH2Cl2 to give 139 mg (48%) of the desired product as an oil. MS: 376.2 (M+1 for C22H27N1O2F2); an oil; TLC (SiO2), Rf 0.73 (8% MeOH/CH2Cl2); HPLC (7:3 CH3CN/H2O with 0.1% TFA, C-18 column) 96.46%, RT=5.448 min.

Workup

  1. washwashed with saturated bicarbonate solution and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was chromatographed twice on silica gel
  5. washeluting with 2-4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-bcf407bd1bf44bbc928721883c0f5200
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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