Benzylamine → N-Benzyl-L-serinamide

HRID 1458397Notes

Reaction equation

HRID 1458397 reaction equation
C([NH:8][C@H:9]([C:12]([OH:14])=O)[CH2:10][OH:11])(OC(C)(C)C)=O.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CCN=C=NCCCN(C)C>CN(C=O)C.CCOC(C)=O>[CH2:32]([NH:39][C:12](=[O:14])[C@H:9]([CH2:10][OH:11])[NH2:8])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 98766N-[tert-butoxycarbonyl]-L-serine

Product 1

HCID 11790078N-Benzyl-L-serinamideYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 4.10 g (20 mmol) of N-Boc-L-serine, 2.97 g (22 mmol) of HOBT, 2.42 mL (22 mmol) of NMM, and 2.40 mL (22 mmol) of benzylamine in 50 mL of anhydrous DMF at 0° C. was added 4.21 g of WSC. The mixture was stirred at 0° C. for 1 h and at room temperature for 3 h. This was then taken up in 300 mL of EtOAc and washed with 100 mL of H2O (2×) and brine (1×). The combined organic layers were dried over MgSO4 and concentrated. After drying under vacuum overnight, the residue was dissolved in 20 mL of CH2 Cl2 and treated with 20 mL of CF3CO2H at 0°-10° C. for ca. 7 h. The solvent and CF3CO2H were removed under vacuum. The trace CF3CO2H was removed azeotropically with CHCl3 at the end. The residue was purified by preparative HPLC, eluting with 8% (10% conc. NH4OH in MeOH)--CH2Cl2 to afford 3.57 g (92%) of the serinamide: mp 97-98° C.; 1H NMR (CDCl3) δ7.82 (br s, 1H), 7.26 (m, 5H), 4.42 (ddd, J=16.7, 15.0, 6.0 Hz, 2H), 3.85 (dd, J=10.8, 5.2 Hz, 1H), 3.70 (dd, J=10.8, 5.3 Hz, 1H), 3.44 (m, 1H), 2.22 (br s, 3H); FDMS 195 (M+1). Anal. (C10H14N2O2) C, H, N.

Workup

  1. washwashed with 100 mL of H2O (2×) and brine (1×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated
  4. customAfter drying under vacuum overnight
  5. dissolutionthe residue was dissolved in 20 mL of CH2 Cl2
  6. additiontreated with 20 mL of CF3CO2H at 0°-10° C. for ca. 7 h
  7. customThe solvent and CF3CO2H were removed under vacuum
  8. customThe trace CF3CO2H was removed azeotropically with CHCl3 at the end
  9. customThe residue was purified by preparative HPLC
  10. washeluting with 8% (10% conc. NH4OH in MeOH)

Sources & evidence

ORD record
ord-a614165da21441288e2b208929215d73
Source dataset
uspto-grants-1998_12
Patent number
US05849766

Reaction notes

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