Diisopropylethylamine → N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine methyl ester

HRID 2370894Notes

Reaction equation

HRID 2370894 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15]([OH:17])=O)[CH2:10][O:11][CH2:12][CH:13]=[CH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20](=[O:33])[C@H:21]([CH:30]([CH3:32])[CH3:31])[NH:22][C:23](=[O:29])[C@H:24]([CH:26]([CH3:28])[CH3:27])[NH2:25].FC(F)(F)C(O)=O.COC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N.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>[CH3:18][O:19][C:20](=[O:33])[C@H:21]([CH:30]([CH3:32])[CH3:31])[NH:22][C:23](=[O:29])[C@H:24]([CH:26]([CH3:27])[CH3:28])[NH:25][C:15](=[O:17])[C@H:9]([CH2:10][O:11][CH2:12][CH:13]=[CH2:14])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11032134(S)-3-(Allyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acidHCID 12944632L-valyl L-valine methyl esterHCID 86671346L-valyl L-valine methyl ester trifluoroacetate

Product 1

HCID 86671348N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine methyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl O-allyl L-serine (3) (11.31 g, 46.10 mmol) was dissolved in 40 mL DMF. A solution of L-valyl L-valine methyl ester.trifluoroacetate 6 (15.87 g, 46.09 mmol) and N,N-diisopropylethyl amine (5.96 g, 46.1 mmol) in 60 mL DMF was added in one portion and the solution cooled to 0° C. (icebath). HOBt hydrate (7.06 g, 46.1 mmol) was added. Finally, EDC hydrochloride (9.72 g, 50.7 mmol) was added together with 30 mL DMF. The reaction mixture was stirred for 22 hours before the solvent was evaporated. The residue was taken up in 250 mL EtOAc and washed with 2 M aqueous H2SO4 (3×100 mL), 7.5% (w/w) aqueous K2CO3 (3×100 mL) and saturated brine (100 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording an off-white solid (19.82 g, 94%); δH (300 MHz; d6-DMSO) 8.18 (1H, d, J 8, NH(Valx), 7.62 (1H, d, J 9, NH(Valy)), 7.03 (1H, d, J 8, NH(Ser(All))), 5.83 (1H, ddt, J 5, 10 and 17, CH═CH2), 5.23 (1H, ddt, J 1, 3 and 17, CH═CHH), 5.11 (1H, ddt, J 1, 3 and 10, CH═CHH), 4.34 (1H, dd, J 7 and 9, CαH(Valy)), 4.22-4.17 (1H, m, CαH(Ser(All))), 4.13 (1H, dd, J 6 and 8, CαH(Valx)), 3.92 (2H, dt, J 1 and 5, CH2CH═CH2), 3.61 (3H, s, OCH3), 3.53-3.49 (2H, m, CH2), 2.11-1.86 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.90-0.79 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.6, 171.0, 169.5, 155.1, 134.9, 116.3, 78.2, 70.9, 69.5, 57.4, 56.8, 54.5, 51.4, 31.1, 29.5, 28.0, 18.9, 18.8, 18.1, 17.7; m/z (ESI) 480.2666 ([M+Na]+; C22H39N3O7Na requires 480.2685)

Workup

  1. customwas evaporated
  2. washwashed with 2 M aqueous H2SO4 (3×100 mL), 7.5% (w/w) aqueous K2CO3 (3×100 mL) and saturated brine (100 mL)
  3. dry with materialThe solution was dried with anhydrous MgSO4
  4. customthe solvent evaporated

Sources & evidence

ORD record
ord-c56380aca82440f5bab2758c0b5df0d3
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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