Diisopropylethylamine → (2S)-N-((1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide

HRID 1874627Notes

Reaction equation

HRID 1874627 reaction equation
[N:1]([CH2:4][C@@H:5]([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)[NH2:6])=[N+:2]=[N-:3].[C:20]1([C@H:26]([CH3:30])[C:27](O)=[O:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=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>[N:1]([CH2:4][C@H:5]([NH:6][C:27](=[O:28])[C@H:26]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:30])[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)=[N+:2]=[N-:3]

Participants

7

Reactant 5

HCID 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 86658398(1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethanamine

Product 1

HCID 86658399(2S)-N-((1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamideYield 92.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethanamine (9.0 g, 34.3 mmol) in dichloromethane (100 mL) was cooled to 0° C. To this solution, (S)-2-phenylpropanoic acid (7.0 mL, 51.5 mmol), N,N-diisopropylethylamine (35.9 mL, 206 mmol) and HATU (19.57 g, 51.5 mmol) were added. The ice 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 (25 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-azido-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (12.5 g, 92% yield) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 7.21-7.34 (m, 5H), 6.98 (d, J=8.6 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.37 (d, J=8.1 Hz, 1H), 5.10 (ddd, J=7.9, 5.8, 5.7 Hz, 1H), 3.76 (dd, J=9.1, 5.8 Hz, 1H), 3.61-3.70 (m, 2H), 3.46-3.56 (m, 2H), 1.87-1.98 (m, 1H), 1.52 (d, J=7.3 Hz, 3H), 1.26-1.51 (m, 3H), 1.21 (dddd, J=12.3, 7.6, 5.3, 5.0 Hz, 1H), 1.01 (d, J=6.5 Hz, 3H), 0.93 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 395.3 [(M+H)+, calcd for C23H31N4O2 395.3].

Workup

  1. customThe ice 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 (25 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-90f7a5b9371f4106bc815229ef8db33e
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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