Dimethylformamide → N-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-4-hydroxy-4-methylpentanamide

HRID 1807718Notes

Reaction equation

HRID 1807718 reaction equation
[CH3:1][C:2]1([CH3:8])[O:6][C:5](=[O:7])[CH2:4][CH2:3]1.C[Al](C)C.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([OH:44])([C:40]([F:43])([F:42])[F:41])[C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=3)[CH2:24][CH2:23]2)=[O:21])=[CH:16][CH:15]=1.CN(C)C=O>C1(C)C=CC=CC=1>[F:42][C:40]([F:41])([F:43])[C:35]([C:32]1[CH:31]=[CH:30][C:29]([CH2:28][N:25]2[CH2:24][CH2:23][N:22]([C:20]([C:17]3[CH:18]=[CH:19][C:14]([NH:13][C:5](=[O:7])[CH2:4][CH2:3][C:2]([OH:6])([CH3:8])[CH3:1])=[CH:15][CH:16]=3)=[O:21])[CH2:27][CH2:26]2)=[CH:34][CH:33]=1)([OH:44])[C:36]([F:39])([F:38])[F:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 18398Iso-caprolactoneHCID 16682925TrimethylaluminumHCID 86638547(4-Aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 86638549N-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-4-hydroxy-4-methylpentanamideYield 0.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5,5-Dimethyldihydrofuran-2(3H)-one (0.433 mmol, 0.049 g) was stirred in toluene (5 mL). Trimethylaluminium (0.867 mmol, 0.867 mL, 1 M in heptane) was added and the reaction stirred for 10 minutes at room temperature. (4-Aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone (0.433 mmol, 0.2 g) was added and the reaction heated to reflux for 1 hour then a drop of N,N-dimethylformamide was added. The reaction mixture was heated to reflux for 1 hour. The reaction mixture was quenched with water. Ethyl acetate was added and the layers separated. The organic phase was concentrated under vacuum and the resulting residue purified by acidic preparative HPLC to afford the desired compound (1 mg).

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 1 hour
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 1 hour
  5. customThe reaction mixture was quenched with water
  6. additionEthyl acetate was added
  7. customthe layers separated
  8. concentrationThe organic phase was concentrated under vacuum
  9. customthe resulting residue purified by acidic preparative HPLC

Sources & evidence

ORD record
ord-aa1005b059134d33b1bc8e79462192c1
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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