Diisopropylethylamine → HCID 76495078, compound

HRID 1953917Notes

Reaction equation

HRID 1953917 reaction equation
[CH3:1][CH:2]([CH3:14])[CH2:3][C@H:4]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[C:5]([OH:7])=O.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.[NH2:49][C@@H:50]([CH2:58][C:59]1[CH:64]=[CH:63][C:62]([O:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)=[CH:61][CH:60]=1)[C:51]([NH:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52]>CN(C=O)C.C(OCC)C>[CH2:66]([O:65][C:62]1[CH:63]=[CH:64][C:59]([CH2:58][CH:50]([NH:49][C:5](=[O:7])[CH:4]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH2:3][CH:2]([CH3:1])[CH3:14])[C:51](=[O:52])[NH:53][C:54]([CH3:55])([CH3:56])[CH3:57])=[CH:60][CH:61]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13765082HCID 13765082, compoundHCID 69584616(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride

Product 1

HCID 76495078HCID 76495078, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-4-Methyl-2-morpholin-4-yl-pentanoic acid (0.161 g, 0.800 mmol) was dissolved in dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added in succession N,N-diisopropyl-ethylamine (0.420 mL, 2.41 mmol) and solid O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (0.303 g, 0.799 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 (0.290 g, 0.800 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 a viscous oil. The crude product was further purified by flash chromatography (60% EtOAc in hexane) and treated with ethereal HCl. Subsequent concentration in vacuo, trituration with ether and drying under vacuum provided 0.27 g (62%) of the pure titled compound as a white 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 a viscous oil
  8. customThe crude product was further purified by flash chromatography (60% EtOAc in hexane)
  9. additiontreated with ethereal HCl
  10. concentrationSubsequent concentration in vacuo, trituration with ether
  11. customdrying under vacuum

Sources & evidence

ORD record
ord-1db6d9462c8848d9bbce871dd443b5b5
Source dataset
uspto-grants-2000_09
Patent number
US06117841

Reaction notes

Loading…