Dimethylformamide → 3-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoylamino]-propionic acid tert-butyl ester

HRID 1953915Notes

Reaction equation

HRID 1953915 reaction equation
C(N[C@H](C(O)=O)CC(C)C)([O:3][CH2:4][CH:5]1C2[C:12](=CC=CC=2)[C:11]2[C:6]1=CC=C[CH:10]=2)=O.C(N(C(C)C)CC)(C)C.CN(C(ON1N=[N:51][C:46]2[CH:47]=[CH:48]C=[CH:50][C:45]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:60]([O:64][C:65](=[O:83])[C@@H:66]([NH2:82])[CH2:67][C:68]1[CH:73]=[CH:72][C:71]([O:74][CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)=[CH:70][CH:69]=1)([CH3:63])([CH3:62])[CH3:61].CN(C=[O:88])C>CCOCC>[C:60]([O:64][C:65](=[O:83])[CH:66]([NH:82][C:4](=[O:3])[CH:5]([NH:51][CH:46]1[CH2:45][CH2:50][O:88][CH2:48][CH2:47]1)[CH2:6][CH:11]([CH3:12])[CH3:10])[CH2:67][C:68]1[CH:73]=[CH:72][C:71]([O:74][CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)=[CH:70][CH:69]=1)([CH3:63])([CH3:61])[CH3:62]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 1549133Fmoc-leucineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11151579tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoate

Product 1

HCID 700696313-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoylamino]-propionic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of FMOC-leucine (10.3 g, 29 mmol) in 300 mL of DMF was cooled to 0° C. and treated with diisopropylethyl amine (73 mL) and HBTU (11.1 g, 29.2 mmol). The resulting solution was stirred at 0° C. for 30 minutes and treated with (S)-2-amino-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester (110 g, 36.9 mmol). The resulting solution was stirred for 30 minutes at 0° C. and warmed to room temperature. The reaction mixture was poured into 500 mL of ether and washed sequentially with IN aqueous HCl, saturated aqueous NaHCO3 (100 mL) and brine (5×100 mL). The organic phase was collected, dried over MgSO4 and concentrated to near dryness. The residue was triturated with hexane. The product was collected by suction filtration and air dried to give the title compound as a white solid (12.16 g, 70%); mp 158-160° C.

Workup

  1. stirringThe resulting solution was stirred for 30 minutes at 0° C.
  2. temperaturewarmed to room temperature
  3. washwashed sequentially with IN aqueous HCl, saturated aqueous NaHCO3 (100 mL) and brine (5×100 mL)
  4. customThe organic phase was collected
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was triturated with hexane
  8. filtrationThe product was collected by suction filtration and air
  9. customdried

Sources & evidence

ORD record
ord-73c711c945d94a228cae6bc8765913d2
Source dataset
uspto-grants-2000_09
Patent number
US06117841

Reaction notes

Loading…