Diisopropylethylamine → N-boc-l-valyl-l-valine methyl ester

HRID 2370889Notes

Reaction equation

HRID 2370889 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:17][O:18][C:19](=[O:25])[C@H:20]([CH:22]([CH3:24])[CH3:23])[NH2:21].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>[CH3:17][O:18][C:19](=[O:25])[C@H:20]([CH:22]([CH3:24])[CH3:23])[NH:21][C:13](=[O:15])[C@H:9]([CH:10]([CH3:11])[CH3:12])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 83693Boc-L-Valine2×HCID 111190Methyl valinate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 13386190N-boc-l-valyl-l-valine methyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl L-valine (28.36 g, 0.1305 mol) was dissolved in DMF (120 mL) and the solution cooled to 0° C. (icebath). L-valine methyl ester hydrochloride (21.88 g, 0.1305 mol) was suspended in DMF (60 mL) and N,N-diisopropylethyl amine (16.87 g, 0.1305 mol) added. The resulting suspension was added to the solution of N-tert-butoxycarbonyl L-valine in one portion. HOBt hydrate (19.99 g, 0.1305 mol) and EDC hydrochloride (27.52 g, 0.1436 mol) were added together with additional DMF (80 mL). After 1 hour the icebath was removed and the reaction mixture stirred for 20 hours. The solvent was evaporated and the residue taken up in EtOAc (600 mL) and washed with 2 M aqueous H2SO4 (3×250 mL), 7.5% (w/w) aqueous K2CO3 (3×250 mL) and saturated brine (200 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (37.50 g, 87%) with spectral characteristics in accordance with literature data2; δH (200 MHz; d6-DMSO) 7.97 (1H, d, J 8, NH(Val2)), 6.68 (1H, d, J 9, NH(Val1)), 4.18 (1H, dd, J 6 and 9, CαH(Val1)), 3.86 (1H, dd, J 8 and 8, CαH(Val2)); 3.61 (3H, s, OCH3), 2.12-1.83 (2H, m, CH(CH3)3), 1.37 (9H, s, (CH3)3), 0.91-0.80 (12H, m, CH3); δC (50 MHz; d6-DMSO) 171.7, 171.7, 155.3, 77.9, 59.4, 57.2, 51.5, 30.2, 29.8, 28.0, 19.0, 18.8, 18.1, 18.1; m/z (ESI) 353.2 ([M+Na]+)

Workup

  1. customAfter 1 hour the icebath was removed
  2. customThe solvent was evaporated
  3. washwashed with 2 M aqueous H2SO4 (3×250 mL), 7.5% (w/w) aqueous K2CO3 (3×250 mL) and saturated brine (200 mL)
  4. dry with materialThe solution was dried with anhydrous MgSO4
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-7e66774823454cbca379355422e83175
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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