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

HRID 2370897Notes

Reaction equation

HRID 2370897 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:18])[CH3:17])[NH2:15].[C:24]([O:28][C:29]([NH:31][C@H:32]([C:42](O)=[O:43])[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].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>[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:17])[CH3:18])[NH:15][C:42](=[O:43])[C@H:32]([CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[NH:31][C:29]([O:28][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:30]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86671346L-valyl L-valine methyl ester trifluoroacetate

Product 1

HCID 86671351N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

L-valyl L-valine methyl ester trifluoroacetate 6 (11.62 g, 33.75 mmol) was dissolved in 60 mL DMF. N-tert-butoxycarbonyl O-benzyl L-serine 14 (9.97 g, 33.8 mmol) was added together with 10 mL DMF. The solution was cooled to 0° C. (icebath) before N,N-diisopropylethyl amine (4.36 g, 33.7 mmol), HOBt hydrate (5.17 g, 33.8 mmol) and EDC hydrochloride (7.12 g, 37.1 mmol) were added together with an additional 30 mL DMF. The reaction mixture was stirred overnight and the solvent evaporated. The residue was taken up in 200 mL EtOAc and washed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a white solid (16.22 g, 95%); δH (300 MHz; d6-DMSO) 8.20 (1H, d, J 8, NH(Valx)), 7.65 (1H, d, J 9, NH(Valy)), 7.35-7.23 (5H, m, Ph), 7.08 (1H, d, J 8, NH(Ser(Bn)), 4.46 (2H, s, CH2Ph), 4.35 (1H, dd, J 7 and 9, CαH(Valy)), 4.25 (1H, m, CαH(Ser(Bn))), 4.12 (1H, dd, J 6 and 8, CαH(Valx)), 3.63-3.54 (2H, m, CH2), 3.60 (3H, s, OCH3), 2.07-1.89 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.88-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.6, 171.0, 169.4, 155.1, 138.0, 128.0, 127.3, 127.3, 78.2, 71.9, 69.8, 57.4, 56.8, 54.5, 51.4, 31.1, 29.5, 28.0, 18.9, 18.7, 18.2, 17.7; m/z (ESI) 530.2824 ([M+Na]+; C26H41N3O7Na requires 530.2842)

Workup

  1. customthe solvent evaporated
  2. washwashed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL)
  3. dry with materialThe solution was dried with anhydrous MgSO4
  4. customthe solvent evaporated

Sources & evidence

ORD record
ord-c8543a77007647dc9aec47fa7aa0063e
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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