N-(tert-butoxycarbonyl)glycine → methyl N-(tert-butoxycarbonyl)glycylglycinate

HRID 2370890Notes

Reaction equation

HRID 2370890 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH2:18].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH:18][C:10](=[O:12])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 637608methyl N-(tert-butoxycarbonyl)glycylglycinateYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-tert-butoxycarbonyl glycine (10.57 g, 60.33 mmol) and glycine methyl ester hydrochloride (7.58 g, 60.4 mmol) were dissolved in DMF (60 mL). N,N-diisopropylethyl amine (7.80 g, 60.4 mmol) and HOBt hydrate (9.24 g, 60.3 mmol) dissolved in DMF (40 mL) were added. The solution was cooled to 0° C. (icebath) and EDC hydrochloride (12.72 g, 66.35 mmol) added in small portions. The reaction mixture was stirred for 15 hours before the solvent was evaporated. The residue was taken up in EtOAc (300 mL) and washed with 2 M aqueous H2SO4 (3×50 mL), 7.5% (w/w) aqueous K2CO3 (3×50 mL) and saturated brine (50 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a clear liquid (10.34 g, 70%) with spectral characteristics in accordance with literature data8; δH (300 MHz; d6-DMSO) 8.17 (1H, t, J 6, NH(Gly2)), 6.97 (1H, t, J 6, NH(Gly1)), 3.85 (2H, d, J 6, CαH2(Gly2)), 3.62 (3H, s, OCH3), 3.57 (2H, d, J 6, CαH2(Gly1)), 1.38 (9H, s, (CH3)3); δC (75 MHz; d6-DMSO) 170.2, 169.9, 155.7, 78.0, 51.6, 42.9, 40.4, 28.1; m/z (ESI) 269.1110 ([M+Na]+; C10H18N2O5 requires 269.1113)

Workup

  1. additionwere added
  2. additionadded in small portions
  3. customwas evaporated
  4. washwashed with 2 M aqueous H2SO4 (3×50 mL), 7.5% (w/w) aqueous K2CO3 (3×50 mL) and saturated brine (50 mL)
  5. dry with materialThe solution was dried with anhydrous MgSO4
  6. customthe solvent evaporated

Sources & evidence

ORD record
ord-65b486ec0b4945e58d6f98663b7bdd50
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

Loading…