Trifluoroacetic acid → HCID 51354469, compound

HRID 1874623Notes

Reaction equation

HRID 1874623 reaction equation
[NH2:1][C@H:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[CH:9][CH:8]=1)[C:3]([CH3:6])([OH:5])[CH3:4].C(O)(C(F)(F)F)=O.[C:27]1([C@H:33]([CH3:37])[C:34](O)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>ClCCl>[OH:5][C:3]([CH3:6])([CH3:4])[C@H:2]([NH:1][C:34](=[O:35])[C@H:33]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:37])[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[CH:11][CH:12]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27246222-Phenylpropionic acid, (+)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67439028HCID 67439028, compound

Product 1

HCID 51354469HCID 51354469, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1R)-1-amino-2-methyl-1-(4-(2-methylpentyloxy)phenyl)propan-2-ol.TFA (100 mg, 0.264 mmol) in dichloromethane (4 mL) was cooled to 0° C. To this solution (S)-2-phenylpropanoic acid (0.043 mL, 0.316 mmol), N,N-diisopropylethylamine (0.276 mL, 1.581 mmol) and HATU (120 mg, 0.316 mmol) were added. The ice-water bath was removed and reaction mixture was stirred at room temperature for 3 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (60 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30%→40% ethyl acetate in hexanes) to afford (2S)-N-((1R)-2-hydroxy-2-methyl-1-(4-(2-methylpentyloxy)phenyl)propyl)-2-phenylpropanamide (73 mg, 70% yield) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 7.17-7.34 (m, 5H), 6.92 (d, J=8.8 Hz, 2H), 6.74 (d, J=8.8 Hz, 2H), 6.29 (d, J=8.6 Hz, 1H), 4.68 (d, J=8.6 Hz, 1H), 3.75 (dd, J=8.8, 5.8 Hz, 1H), 3.59-3.68 (m, 2H), 1.90 (dq, J=12.9, 6.4 Hz, 1H), 1.74 (s, 1H), 1.47 (d, J=7.1 Hz, 3H), 1.26-1.51 (m, 3H), 1.18 (s, 3H), 1.14-1.26 (m, 1 H), 0.98 (d, J=6.5 Hz, 3H), 0.96 (s, 3H), 0.90 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 398.2 [(M+H)+, calcd for C25H36NO3 398.3].

Workup

  1. customThe ice-water bath was removed
  2. customreaction mixture
  3. customThe reaction mixture was transferred to a separatory funnel
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (30%→40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6b1b1edcb6b946e08b1a0b4a15e50ea7
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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