Sulfuric Acid → (R)-5,5,5-trifluoro-2-(((R)-1-phenylethyl)amino)pentanamide hydrochloride

HRID 660264Notes

Reaction equation

HRID 660264 reaction equation
[F:1][C:2]([F:18])([F:17])[CH2:3][CH2:4][CH:5]([NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:6]#[N:7].[OH:19]S(O)(=O)=O.[NH4+].[OH-].C(Cl)[Cl:27]>>[ClH:27].[F:1][C:2]([F:17])([F:18])[CH2:3][CH2:4][C@@H:5]([NH:8][C@@H:9]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:10])[C:6]([NH2:7])=[O:19]

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 66649793Pentanenitrile, 5,5,5-trifluoro-2-[[(1R)-1-phenylethyl]amino]-

Product 1

HCID 66649708(R)-5,5,5-trifluoro-2-(((R)-1-phenylethyl)amino)pentanamide hydrochloride

Procedure

To a solution of 5,5,5-trifluoro-2-(1-phenylethylamino)pentanenitrile (18.0 g, 70.31 mmol, 4:1 mixture of diastereomers) in CH2Cl2 (100 mL) was added H2SO4 (100 mL). The reaction was stirred at room temperature for 22 h, poured onto crushed ice and neutralized with NH4OH. The mixture was extracted with EtOAc (3×500 mL). The combined organic layer was dried over Na2SO4 and concentrated under vacuum to provide the free base of the title compound as a mixture of diastereomers (18.94 g, 98%) as an orange oil: 1H NMR (300 MHz, CDCl3) δ 7.40-7.18 (m, 5H), 6.78 (br s, 0.23H), 6.50 (br s, 0.77H), 6.00 (br s, 0.77H), 5.81 (br s, 0.23H), 3.82 (q, J=6.5 Hz, 0.23H), 3.70 (q, J=6.5 Hz, 0.77H), 3.14 (t, J=6.0 Hz, 0.23H), 2.86 (t, J=7.0 Hz, 0.77H), 2.35-1.86 (m, 2H), 1.84-1.64 (m, 2H), 1.39 (d, J=6.5 Hz, 0.69H), 1.35 (d, J=6.5 Hz, 2.31H); ESI MS m/z 275 [C13H17F3N2O+H].

Workup

  1. additionpoured
  2. customonto crushed ice
  3. extractionThe mixture was extracted with EtOAc (3×500 mL)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-a8bc6757731c45118266e9fd0c02e24f
Source dataset
uspto-grants-2011_12
Patent number
US08084477B2

Reaction notes

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