Diethyl acetylenedicarboxylate → 3-[2-(1,1-Dioxo-1lambda6-[1,2]thiazinan-2-yl)-phenyl]-5-ethoxycarbonylmethyl-2-methyl-2,5-dihydro-[1,2,4]oxadiazole-5-carboxylic acid ethyl ester

HRID 1822720Notes

Reaction equation

HRID 1822720 reaction equation
[O:1]=[S:2]1(=[O:19])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:18]=[CH:17][CH:16]=[CH:15][C:9]=1[C:10]([N:12]([OH:14])[CH3:13])=[NH:11].[C:20]([C:27]([O:29][CH2:30][CH3:31])=[O:28])#[C:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>C(O)C>[CH2:30]([O:29][C:27]([C:20]1([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[O:14][N:12]([CH3:13])[C:10]([C:9]2[CH:15]=[CH:16][CH:17]=[CH:18][C:8]=2[N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][S:2]2(=[O:1])=[O:19])=[N:11]1)=[O:28])[CH3:31]

Participants

4

Reactant 2

HCID 69803Diethyl acetylenedicarboxylateHCID 235683992-(1,1-Dioxo-1lambda6-[1,2]thiazinan-2-yl)-N-hydroxy-N-methyl-benzamidine

Product 1

HCID 235684153-[2-(1,1-Dioxo-1lambda6-[1,2]thiazinan-2-yl)-phenyl]-5-ethoxycarbonylmethyl-2-methyl-2,5-dihydro-[1,2,4]oxadiazole-5-carboxylic acid ethyl esterYield 64.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 2-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-N-hydroxy-N-methyl-benzamidine (3.5 g) in ethanol (100 mL, 200 proof) was added diethyl acetylene-dicarboxylate (3.2 mL, 20 mmol) and the resulting mixture stirred at room temperature for 30 min. The mixture was concentrated and purified on a silica gel column (10%–30% ethyl acetate/hexanes) to afford the title compound as a yellow oil (3.62 g, 40% yield). 1HNMR (300 MHz, CDCl3) δ: 7.57 (2H, td, J=7.14, 1.28 Hz,), 7.50 (1H, td, J=7.68, 1.83 Hz), 7.39 (1H, td, J=7.50, 1.46 Hz), 4.34–4.22 (2H, m), 4.18 (2H, q, J=7.08 Hz), 3.42 (1H, d, J=16.47 Hz), 3.22–3.18 (2H, m), 3.07 (3H, s), 3.05 (1H, d, J=16.46 Hz), 2.38–2.24 (2H, m), 2.00–1.42 (2H, m), 1.33 (3H, t, J=7.14 Hz), 1.26 (3H, t, J=7.14 Hz). HRMS calcd for C20H28SN3O7 (M+H): 454.1648; found: 454.1650.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified on a silica gel column (10%–30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-032ebde4e19b48e5adc17eba1c36fcd4
Source dataset
uspto-grants-2006_05
Patent number
US07037908B2

Reaction notes

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