Dichloromethane → 2-(((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamoyl)-4-methoxypyridin-3-yl isopropyl carbonate

HRID 75758Notes

Reaction equation

HRID 75758 reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH:19](O)[CH3:20])[C@H:15]([CH3:22])[O:14][C:13](=[O:23])[C@@H:12]([NH:24][C:25](=[O:35])[C:26]2[C:31]([OH:32])=[C:30]([O:33][CH3:34])[CH:29]=[CH:28][N:27]=2)[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38].[CH2:43](Cl)Cl>CN(C1C=CN=CC=1)C>[C:37](=[O:38])([O:39][CH:40]([CH3:42])[CH3:41])[O:32][C:31]1[C:26]([C:25](=[O:35])[NH:24][C@H:12]2[CH2:11][O:10][CH2:9][C@H:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C@@H:16]([O:17][CH2:18][CH:19]([CH3:20])[CH3:43])[C@H:15]([CH3:22])[O:14][C:13]2=[O:23])=[N:27][CH:28]=[CH:29][C:30]=1[O:33][CH3:34]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 7917Isopropyl chloroformateHCID 86701254N-((3S,7S,8R,9S)-7-benzyl-8-(2-hydroxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide

Product 1

HCID 867012532-(((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamoyl)-4-methoxypyridin-3-yl isopropyl carbonateYield 44%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution of N-((3S,7S,8R,9S)-7-benzyl-8-(2-hydroxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (160 mg, 0.33 mmol) in CH2Cl2 (2 mL) were added isopropyl chloroformate (44 mg, 0.36 mmol) and DMAP (44 mg, 0.36 mmol) at 0° C., and the solution was allowed to warm to room temperature overnight. The crude reaction mixture was concentrated and the residue purified via flash chromatography (SiO2, 50% EtOAc/hexanes) to furnish the product (83 mg, 44%) as white foam: IR (film) 3375, 2956, 2874, 1762, 1680 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J=8.4 Hz, 1H), 8.32 (d, J=5.4 Hz, 1H), 7.33-7.24 (m, 2H), 7.20 (dd, J=7.2, 5.3 Hz, 3H), 7.00 (d, J=5.5 Hz, 1H), 5.08-4.91 (m, 3H), 4.01 (dd, J=11.7, 7.4 Hz, 1H), 3.92 (s, 3H), 3.50-3.42 (m, 3H), 3.37-3.30 (m, 2H), 3.17-3.11 (m, 2H), 2.37-2.29 (m, 1H), 2.00-1.83 (m, 2H), 1.49 (d, J=6.4 Hz, 3H), 1.41 (d, J=6.3 Hz, 6H), 0.97-0.93 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 171.79, 162.53, 159.38, 152.03, 146.81, 141.44, 140.03, 137.78, 129.20 (2), 128.43 (2), 126.09, 110.03, 84.53, 79.27, 75.68, 73.76, 72.31, 71.92, 56.32, 51.44, 47.43, 35.09, 29.19, 21.71 (2), 19.50 (2), 18.79; ESIMS m/z 574.39 ([M+H]+).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated
  3. customthe residue purified via flash chromatography (SiO2, 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b8dcd6a4a7494934b7b33ad019824d35
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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