Methyl propiolate → (E)-methyl 3-((3S,6S,7R,8S)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4-oxo-1,5-dioxonan-7-yloxy)acrylate

HRID 75744

Reaction equation

HRID 75744 reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([OH:17])[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([O:32][CH3:33])(=[O:31])[C:29]#[CH:30]>C(Cl)Cl.C1N2CCN(CC2)C1>[CH2:1]([C@H:8]1[CH2:9][O:10][CH2:11][C@H:12]([NH:20][C:21]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:27])[C:13](=[O:19])[O:14][C@@H:15]([CH3:18])[C@@H:16]1[O:17]/[CH:30]=[CH:29]/[C:28]([O:32][CH3:33])=[O:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 13536Methyl propiolateHCID 86701245tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

Product 1

HCID 86701238(E)-methyl 3-((3S,6S,7R,8S)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4-oxo-1,5-dioxonan-7-yloxy)acrylateYield 91.2%

Reagents, catalysts & solvents 2

HCID 9237DabcoCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo−1,5-dioxonan-3-yl)carbamate (280 mg, 0.738 mmol, 1.00 equiv) in CH2Cl2 (7.4 mL) were added methyl propiolate (0.098 mL, 1.11 mmol, 1.50 equiv) and DABCO (4 mg, 0.04 mmol, 0.05 equiv). This solution was stirred at room temperature for 1 h, concentrated, and purified by automated silica gel column chromatography (5-25% acetone in hexanes) to provide (E)-methyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate (312 mg, 91%) as a white solid: mp slow melt from 50-80° C., recrystallized at 98° C., remelt at 128-129° C.; IR (neat film) 3342, 2980, 2949, 1753, 1703, 1639, 1497, 1329, 1132, 910, 731 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J=12.2 Hz, 1H), 7.32-7.27 (m, 2H), 7.23-7.18 (m, 1H), 7.15-7.11 (m, 2H), 5.40 (d, J=12.2 Hz, 1H), 5.10 (d, J=8.3 Hz, 1H), 5.02 (dd, J=9.3, 6.4 Hz, 1H), 4.64 (dd, J=15.3, 7.5 Hz, 1H), 3.92 (dd, J=11.6, 7.6 Hz, 1H), 3.74 (d, J=9.1 Hz, 1H), 3.71 (s, 3H), 3.51 (d, J=11.1 Hz, 1H), 3.43 (dd, J=10.5, 6.4 Hz, 1H), 3.29 (dd, J=11.3, 7.5 Hz, 1H), 2.92 (dd, J=13.8, 3.5 Hz, 1H), 2.34 (t, J=12.5 Hz, 1H), 2.06 (s, 1H), 1.42 (s, 9H), 1.41 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.16, 167.97, 162.94, 154.91, 138.54, 129.09, 128.57, 126.48, 98.50, 89.01, 80.31, 73.94, 72.57, 71.33, 52.70, 51.26, 46.47, 35.18, 28.25, 18.73; HRMS-ESI (m/z) [M+Na]+ calc'd for C24H33NO8Na, 486.2098. found, 486.2104.

Workup

  1. concentrationconcentrated
  2. custompurified by automated silica gel column chromatography (5-25% acetone in hexanes)

Sources & evidence

ORD record
ord-e266892eddf2426eacbd461f541d60db
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Linked notes

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