3-Methoxypropanoyl chloride → HCID 86701333, compound

HRID 2283022Notes

Reaction equation

HRID 2283022 reaction equation
[CH2:1]([O:5][C@@H:6]1[C@@H:14]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C@H:13]([CH3:20])[O:12][C:11](=[O:21])[C@@H:10]([NH:22][C:23](=[O:33])[C:24]2[C:29]([OH:30])=[C:28]([O:31][CH3:32])[CH:27]=[CH:26][N:25]=2)[CH2:9][O:8][CH2:7]1)[CH:2]([CH3:4])[CH3:3].[CH3:34][O:35][CH2:36][CH2:37][C:38](Cl)=[O:39]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:34][O:35][CH2:36][CH2:37][C:38]([O:30][C:29]1[C:24]([C:23](=[O:33])[NH:22][C@H:10]2[CH2:9][O:8][CH2:7][C@H:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])[C@@H:14]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C@H:13]([CH3:20])[O:12][C:11]2=[O:21])=[N:25][CH:26]=[CH:27][C:28]=1[O:31][CH3:32])=[O:39]

Participants

5

Reactant 2

HCID 27597283-Methoxypropanoyl chlorideHCID 86701299HCID 86701299, compound

Product 1

HCID 86701333HCID 86701333, compoundYield 94.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A reaction flask was charged with N-((3S,7S,8S,9S)-7,8-diisobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (97 mg, 0.207 mmol), DMAP (40.1 mg, 0.328 mmol), and DCM. 3-Methoxypropanoyl chloride (22.5 μl, 0.207 mmol) was added and the colorless solution was stirred at room temperature under N2 overnight. The reaction mixture was concentrated and purified by column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (108.5 mg, 94% yield) as a sticky orange oil: IR (thin film) 3375, 2955, 2873, 1753, 1677, 1507, 1088 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.67 (d, J=8.2 Hz, 1H), 8.38-8.30 (m, 1H), 7.00 (dd, J=5.7, 1.8 Hz, 1H), 5.08-4.98 (m, 1H), 4.93 (ddt, J=12.2, 8.4, 4.1 Hz, 1H), 4.00 (tt, J=7.2, 3.4 Hz, 1H), 3.93-3.84 (m, 3H), 3.85-3.64 (m, 5H), 3.64-3.55 (m, 1H), 3.41 (d, J=1.5 Hz, 3H), 3.33-3.12 (m, 5H), 2.97 (t, J=6.6 Hz, 2H), 1.82 (tt, J=12.9, 6.0 Hz, 2H), 1.43 (dd, J=6.3, 1.7 Hz, 3H), 0.97-0.85 (m, 12H); 13C NMR (101 MHz, CDCl3) δ 170.85, 169.37, 162.67, 159.42, 146.81, 141.19, 137.38, 109.88, 84.82, 83.75, 80.56, 77.70, 74.88, 74.07, 72.99, 67.58, 58.80, 56.32, 52.13, 34.61, 29.11, 28.87, 19.58, 19.46, 19.37, 18.63; ESIMS m/z 555 ([M+H]+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by column chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-6ebf19349ceb44eb98356ed8a82815f0
Source dataset
uspto-grants-2015_09
Patent number
US09144239B2

Reaction notes

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