3-Methoxypropanoyl chloride → HCID 86701333, compound

HRID 1627055Notes

Reaction equation

HRID 1627055 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-9e8aca3e43ef4e6b9b80f28d2f367d88
Source dataset
uspto-grants-2014_07
Patent number
US08785479B2

Reaction notes

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