Triethylamine → 2(S)-{2(R)-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoylamino}-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

HRID 2230296Notes

Reaction equation

HRID 2230296 reaction equation
[N:1]1([C:8]([NH:10][C@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:50]([O:54][C:55](=[O:73])[C@@H:56]([NH2:72])[CH2:57][C:58]1[CH:63]=[CH:62][C:61]([O:64][CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)=[CH:60][CH:59]=1)([CH3:53])([CH3:52])[CH3:51]>C(#N)C>[C:50]([O:54][C:55](=[O:73])[C@@H:56]([NH:72][C:12](=[O:14])[C@H:11]([NH:10][C:8]([N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:9])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:57][C:58]1[CH:63]=[CH:62][C:61]([O:64][CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)=[CH:60][CH:59]=1)([CH3:53])([CH3:51])[CH3:52]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11151579tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoateHCID 12017803(R)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid

Product 1

HCID 129685682(S)-{2(R)-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoylamino}-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl esterYield 86.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of the product from Example AA ((R)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid) (1.0 g, 3.9 mmol) and triethylamine (1.1 mL, 7.8 mmol) in acetonitrile (15 mL) was treated with HBTU (1.54 g, 4.06 mmol). The resulting solution was treated with the product from Example A ((S)-2-amino-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester) (1.33 g, 4.06 mmol), and the resulting solution was stirred at room temperature for 30 minutes and allowed to stand overnight. The reaction mixture was concentrated and the residue dissolved in ethyl acetate (100 mL) and washed sequentially with 0.6 M aqueous NaHCO3 solution, saturated aqueous NaCl solution, and water. The organic phase was dried over MgSO4 and activated charcoal, filtered, and concentrated. The residue was purified by chromatography (silica gel, 25% ethyl acetate/hexane) to give the title compound as a white solid (1.9 g, 86%), mp=64-66° C.

Workup

  1. waitto stand overnight
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue dissolved in ethyl acetate (100 mL)
  4. washwashed sequentially with 0.6 M aqueous NaHCO3 solution, saturated aqueous NaCl solution, and water
  5. dry with materialThe organic phase was dried over MgSO4 and activated charcoal
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (silica gel, 25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-27a146029786496f9ac9053e40456315
Source dataset
uspto-grants-2002_07
Patent number
US06423689B1

Reaction notes

Loading…