4-Methylmorpholine → 3-allyloxycarbonylamino-N-methoxy-N-methyl-succinamic acid tert-butyl ester

HRID 1824432Notes

Reaction equation

HRID 1824432 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][CH:8]([NH:12][C:13]([O:15][CH2:16][CH:17]=[CH2:18])=[O:14])[C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:21][O:22][NH:23][CH3:24].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:1]([O:5][C:6](=[O:19])[CH2:7][CH:8]([NH:12][C:13]([O:15][CH2:16][CH:17]=[CH2:18])=[O:14])[C:9]([N:23]([O:22][CH3:21])[CH3:24])=[O:11])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 235986592-Allyloxycarbonylamino-succinic acid 4-tert-butyl ester

Product 1

HCID 235987113-allyloxycarbonylamino-N-methoxy-N-methyl-succinamic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Allyloxycarbonylamino-succinic acid 4-tert-butyl ester, 100, (43.4 g, 0.159 mol) is dissolved in CH2Cl2(900 mL). To this solution O,N-dimethyl-hydroxylamine hydrochloride (18.6 g, 0.191 mol), 4-Methyl-morpholine (21.0 mL, 19.3 g, 0.191 mol), and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (36.6 g, 0.191 mol) are added. After the consumption of the starting material, the solution is washed with 1.0 N HCl (2×400 mL) and brine (1×250 mL). The organic layer is concentrated in vacuo and the residue purified over silica (hexanes/ethyl acetate 65:35) to afford 40.8 g (81% yield) of the desired product as a clear oil. 1H-NMR, (300 MHz, CDCl3): δ 1.43 (s, 9H), 2.50–2.74 (m, 2H), 3.22 (s, 3H), 3.79 (s, 3H), 4.55–4.57 (d, J=4.8, 2H), 4.97–5.04 (m, 1H), 5.17–5.32 (m, 2H), 5.67–5.70 (d, J=9.0, 1H), 5.83–5.94 (m, 1H); 13C-NMR (75.5 MHz, CDCl3): δ 28.20, 32.58, 38.48, 61.83, 65.93, 81.53, 117.85, 132.88, 155.84, 169.46, 171.83; MS (ESI): m/e=317.11 (M+H).

Workup

  1. customAfter the consumption of the starting material
  2. washthe solution is washed with 1.0 N HCl (2×400 mL) and brine (1×250 mL)
  3. concentrationThe organic layer is concentrated in vacuo
  4. customthe residue purified over silica (hexanes/ethyl acetate 65:35)

Sources & evidence

ORD record
ord-3899804b958845dba65e0e9f75722f0f
Source dataset
uspto-grants-2006_05
Patent number
US07041696B2

Reaction notes

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