Diisopropylethylamine → HCID 49823979, compound

HRID 1953919Notes

Reaction equation

HRID 1953919 reaction equation
Br.[CH3:2][CH:3]([CH3:15])[CH2:4][C@H:5]([N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[C:6]([OH:8])=O.Cl.[NH2:17][C@@H:18]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:29][CH:28]=1)[C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.N[C@@H](CC1C=CC(OCC2C=CC=CC=2)=CC=1)C(NC(C)(C)C)=O>C(OCC)C.CN(C=O)C>[CH2:34]([O:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][CH:18]([NH:17][C:6](=[O:8])[CH:5]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:4][CH:3]([CH3:2])[CH3:15])[C:19](=[O:20])[NH:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[CH:28][CH:29]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69584616(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochlorideHCID 131721994HCID 131721994, compound

Product 1

HCID 49823979HCID 49823979, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (S)-4-Methyl-2-piperidin-1-yl-pentanoic acid monohydrobromide (0.493 g, 1.76 mmol) was mixed with dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this mixture were added in succession N,N-diisopropylethylamine (1.23 mL, 7.05 mmol ) and solid O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (0.667 g, 1.76 mmol ). The resulting reaction mixture was stirred at that temperature for 30 minutes, solid (S)-2-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (0.639 g, 1.76 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 45 minutes at ambient temperature, reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording an viscous oil. The crude product was further purified by flash chromatography (40% EtOAc in hexane). Recrystallization from EtOAC/hexanes and subsequent drying under vacuum provided 0.4 g (45%) of the pure titled compound as a white crystalline solid.

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
  3. custom45 minutes at ambient temperature, reaction mixture
  4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL)
  5. dry with materialwas dried over Na2SO4
  6. concentrationThe solution was concentrated in vacuo
  7. customaffording an viscous oil
  8. customThe crude product was further purified by flash chromatography (40% EtOAc in hexane)
  9. customRecrystallization from EtOAC/hexanes
  10. customsubsequent drying under vacuum

Sources & evidence

ORD record
ord-15dc65ece1e2453fbb8eee43e9b2ba45
Source dataset
uspto-grants-2000_09
Patent number
US06117841

Reaction notes

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