Tetrahydrofuran → (αS)-α-[Bis(phenylmethyl)amino]-4-(trifluoromethyl)benzenepropanal

HRID 661113Notes

Reaction equation

HRID 661113 reaction equation
[CH2:1]([N:8]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:9]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[C:10](N(OC)C)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOC(C)=O>[CH2:27]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[CH:10]=[O:11])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 21226445Aluminium lithium hydrideHCID 57634048HCID 57634048, compound

Product 1

HCID 57634167(αS)-α-[Bis(phenylmethyl)amino]-4-(trifluoromethyl)benzenepropanalYield 83.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 500 mL round-bottomed flask was added (S)-2-(dibenzylamino)-N-methoxy-N-methyl-3-(4-(trifluoromethyl)phenyl)propanamide (6.22 g, 13.6 mmol), THF (100 mL), and LAH, 1.0 M solution in THF (27.3 mL, 27.3 mmol), dropwise at 0° C. After 30 minutes, TLC (2:1 hexanes:EtOAc) showed that no starting material remained. The mixture was quenched by dropwise addition of water (6.82 mL), 2 N NaOH (6.82 mL), and water (9.83 mL). The solids were removed by filtration through a medium scintered glass funnel. The filtrate was dried over sodium sulfate and evaporated. The residue was taken up in EtOAc (200 mL) and washed with brine (50 mL). The organic layer was dried over sodium sulfate and evaporated to provide (S)-2-(dibenzylamino)-3-(4-(trifluoromethyl)phenyl)propanal (4.51 g, 83.3% yield) as a light yellow oil. LCMS (ES+) m/z=398.2. 1H NMR (400 MHz, CDCl3) δ ppm 2.96 (dd, J=13.89, 5.67 Hz, 1H) 3.18 (dd, J=13.89, 7.43 Hz, 1H) 3.52-3.55 (m, 1H) 3.66-3.72 (m, 2H) 3.82-3.88 (m, 2H) 7.21-7.33 (m, 12H) 7.50 (d, J=8.02 Hz, 2H) 9.74 (s, 1H).

Workup

  1. customdropwise at 0° C
  2. customThe mixture was quenched by dropwise addition of water (6.82 mL), 2 N NaOH (6.82 mL), and water (9.83 mL)
  3. customThe solids were removed by filtration through a medium
  4. dry with materialThe filtrate was dried over sodium sulfate
  5. customevaporated
  6. washwashed with brine (50 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-929ac3cd476f42bdb3ba6ed14446f3ec
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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