Acetyl chloride → (3S,6S,7R,8S)-3-(3-acetoxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate

HRID 58964Notes

Reaction equation

HRID 58964 reaction equation
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][CH2:12][C@H:11]([NH:27][C:28](=[O:38])[C:29]2[C:34]([OH:35])=[C:33]([O:36][CH3:37])[CH:32]=[CH:31][N:30]=2)[C:10](=[O:39])[O:9][C@H:8]1[CH3:40])(=[O:5])[CH:2]([CH3:4])[CH3:3].[C:41](Cl)(=[O:43])[CH3:42]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][CH2:12][C@H:11]([NH:27][C:28](=[O:38])[C:29]2[C:34]([O:35][C:41](=[O:43])[CH3:42])=[C:33]([O:36][CH3:37])[CH:32]=[CH:31][N:30]=2)[C:10](=[O:39])[O:9][C@H:8]1[CH3:40])(=[O:5])[CH:2]([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 117974378(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate

Product 1

HCID 117974758(3S,6S,7R,8S)-3-(3-acetoxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrateYield 93.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate (80 mg, 0.145 mmol) and DMAP (28.4 mg, 0.232 mmol) in CH2Cl2 (1.45 mL) was added acetyl chloride (218 μL, 0.218 mmol) slowly and the resulting mixture was stirred at room temperature for 14 h. The reaction mixture was treated with Celite®, the solvent removed under reduced pressure, and the resulting adsorbed crude material was purified by flash chromatography (SiO2, 0→100% acetone/hexanes) to afford (3S,6S,7R,8S)-3-(3-acetoxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate as a white powder (80 mg, 93%): mp 104-108° C.; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J=8.2 Hz, 1H), 8.27 (d, J=5.4 Hz, 1H), 8.01-7.94 (m, 1H), 7.88-7.81 (m, 1H), 7.73 (d, J=8.2 Hz, 1H), 7.55-7.43 (m, 2H), 7.39 (dd, J=8.2, 7.0 Hz, 1H), 7.29 (dd, J=7.0, 1.2 Hz, 1H), 6.96 (d, J=5.4 Hz, 1H), 5.18-5.02 (m, 3H), 4.00 (dd, J=11.7, 7.4 Hz, 1H), 3.86 (s, 3H), 3.58 (d, J=4.2 Hz, 2H), 3.37 (dd, J=11.7, 7.2 Hz, 1H), 3.22 (dd, J=14.1, 3.1 Hz, 1H), 2.76-2.63 (m, 2H), 2.38 (s, 3H), 2.34-2.22 (m, 1H), 1.38 (d, J=5.7 Hz, 3H), 1.29 (d, J=3.7 Hz, 3H), 1.27 (d, J=3.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 176.38, 171.66, 168.84, 162.67, 159.42, 146.73, 141.03, 137.53, 134.77, 133.99, 131.98, 128.97, 127.78, 127.34, 126.01, 125.57, 125.39, 123.50, 109.95, 77.05, 74.20, 72.26, 71.84, 56.29, 51.51, 44.99, 34.38, 32.26, 20.73, 19.15, 19.08, 18.28; HRMS-ESI (m/z) [M+H]+ calcd for C32H37N2O9 expected, 593.2494. found, 593.2502.

Workup

  1. additionThe reaction mixture was treated with Celite®
  2. customthe solvent removed under reduced pressure
  3. customthe resulting adsorbed crude material was purified by flash chromatography (SiO2, 0→100% acetone/hexanes)

Sources & evidence

ORD record
ord-888dc95ad6ce4168b9864a224896ec65
Source dataset
uspto-grants-2016_09
Patent number
US09439422B2

Reaction notes

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