Acetyl chloride → HCID 86701334, compound

HRID 1627057Notes

Reaction equation

HRID 1627057 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][C:5]([O:6][C@@H:7]2[C@@H:15]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C@H:14]([CH3:24])[O:13][C:12](=[O:25])[C@@H:11]([NH:26][C:27](=[O:37])[C:28]3[C:33]([OH:34])=[C:32]([O:35][CH3:36])[CH:31]=[CH:30][N:29]=3)[CH2:10][O:9][CH2:8]2)=[CH:4][CH:3]=1.[C:40](Cl)(=[O:42])[CH3:41]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:40]([O:34][C:33]1[C:28]([C:27](=[O:37])[NH:26][C@H:11]2[CH2:10][O:9][CH2:8][C@H:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:39][CH:38]=3)[C@@H:15]([O:16][C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C@H:14]([CH3:24])[O:13][C:12]2=[O:25])=[N:29][CH:30]=[CH:31][C:32]=1[O:35][CH3:36])(=[O:42])[CH3:41]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 86701335N-((3S,7S,8S,9S)-7,8-bis(4-fluorophenoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide

Product 1

HCID 86701334HCID 86701334, compoundYield 80.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-((3S,7S,8S,9S)-7,8-bis(4-fluorophenoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (54 mg, 0.099 mmol) in DCM (0.5 mL) was added TEA (0.028 mL, 0.198 mmol), DMAP (6.1 mg, 0.050 mmol), and acetyl chloride (0.011 ml, 0.149 mmol). The reaction was warmed to 40° C. for and stirred for 14 h. The reaction was then concentrated and the crude residue purified by flash chromatography (SiO2, EtOAc/Hexanes) to give the title compound as a white foam (46.5 mg, 80%): IR (thin film) 3372, 2939, 1765, 1676 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J=8.2 Hz, 1H), 8.37 (d, J=5.4 Hz, 1H), 7.03 (d, J=5.5 Hz, 1H), 6.98-6.86 (m, 6H), 6.74-6.61 (m, 2H), 5.33-5.24 (m, 1H), 5.14 (m, 1H), 4.36 (t, J=9.2 Hz, 1H), 4.30-4.22 (m, 1H), 4.10-3.99 (m, 2H), 3.92 (s, 3H), 3.92-3.87 (m, 1H), 3.79 (dd, J=11.2, 7.3 Hz, 1H), 2.40 (s, 3H), 1.48 (d, J=6.4 Hz, 3H); HRMS-FAB (m/z) [M+H]+ calcd for C29H28F2N2O9, 587.1836; found, 587.1838.

Workup

  1. concentrationThe reaction was then concentrated
  2. customthe crude residue purified by flash chromatography (SiO2, EtOAc/Hexanes)

Sources & evidence

ORD record
ord-4f10771d838842b78fbc335eaeb01afc
Source dataset
uspto-grants-2014_07
Patent number
US08785479B2

Reaction notes

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