Diisopropylethylamine → (S)-N-Benzyl-2-hydroxy-N-((R)-3,3,3-trifluoro-2-hydroxypropyl)propanamide

HRID 922772Notes

Reaction equation

HRID 922772 reaction equation
[CH2:1]([NH:8][CH2:9][C@@H:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C@@H:26]([CH3:30])[C:27](O)=[O:28].C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)[O:35]1)CC>CC#N>[CH2:1]([N:8]([CH2:9][C@@H:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[C:27](=[O:28])[C@@H:26]([OH:35])[CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 107915(S)-(-)-2-Chloropropionic acidHCID 111923Propylphosphonic anhydrideHCID 1477381(R)-3-Benzylamino-1,1,1-trifluoro-propan-2-ol

Product 1

HCID 89544014(S)-N-Benzyl-2-hydroxy-N-((R)-3,3,3-trifluoro-2-hydroxypropyl)propanamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-3-(benzylamino)-1,1,1-trifluoropropan-2-ol (4-2, 5 g, 22.81 mmol) in CH3CN (200 ml) was added DIEA (12 ml, 68.7 mmol), (S)-2-chloropropionic acid (2.4 ml, 27.4 mmol), then 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (16.3 ml, 27.4 mmol) slowly at rt. After 2.5 hr the mixture was concentrated. The material was taken up in EtOAc and washed with saturated NaHCO3, H2O, and brine. The organic layer was filtered through a pad of silica gel washing with ethyl acetate then concentrated to afford (S)—N-benzyl-2-hydroxy-N—((R)-3,3,3-trifluoro-2-hydroxypropyl)propanamide (4-3) as a clear oil which was sufficiently pure for use in the next step.

Workup

  1. customslowly at rt
  2. concentrationAfter 2.5 hr the mixture was concentrated
  3. washwashed with saturated NaHCO3, H2O, and brine
  4. filtrationThe organic layer was filtered through a pad of silica gel washing with ethyl acetate
  5. concentrationthen concentrated

Sources & evidence

ORD record
ord-659d4730caeb4f299b8100e30d06d7a5
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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