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

HRID 58962

Reaction equation

HRID 58962 reaction equation
[Cl-].[C:2]([O:7][C@H:8]1[C@H:16]([CH3:17])[O:15][C:14](=[O:18])[C@@H:13]([NH3+:19])[CH2:12][O:11][CH2:10][C@@H:9]1[CH2:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23][CH:22]=1)(=[O:6])[CH:3]([CH3:5])[CH3:4].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[OH:64][C:65]1[C:66]([C:73](O)=[O:74])=[N:67][CH:68]=[CH:69][C:70]=1[O:71][CH3:72].C(N(C(C)C)C(C)C)C>C(Cl)Cl>[C:2]([O:7][C@@H:8]1[C@@H:9]([CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)[CH2:10][O:11][CH2:12][C@H:13]([NH:19][C:73](=[O:74])[C:66]2[C:65]([OH:64])=[C:70]([O:71][CH3:72])[CH:69]=[CH:68][N:67]=2)[C:14](=[O:18])[O:15][C@H:16]1[CH3:17])(=[O:6])[CH:3]([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 110411213-Hydroxy-4-methoxypyridine-2-carboxylic acidHCID 117974668(3S,7S,8R,9S)-8-(isobutyryloxy)-9-methyl-7-(naphthalen-1-ylmethyl)-2-oxo-1,5-dioxonan-3-aminium chloride

Product 1

HCID 117974378(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrateYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (3S,7S,8R,9S)-8-(isobutyryloxy)-9-methyl-7-(naphthalen-1-ylmethyl)-2-oxo-1,5-dioxonan-3-aminium chloride in CH2Cl2 (2 mL) were added PyBOP (248 mg, 0.477 mmol) and 3-hydroxy-4-methoxypicolinic acid (81 mg, 0.477 mmol) followed by the dropwise addition of N-ethyl-N-isopropylpropan-2-amine (249 μL, 1.43 mmol). After 10 min everything solubilized and stirring was continued for 2 h. The reaction was treated with Celite®, the solvent removed under reduced pressure, and the resulting adsorbed crude material was purified by flash chromatography (SiO2, 0→100% EtOAc/hexanes) to provide (3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolin-amido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-yl isobutyrate as a white powder (210 mg, 88%): mp 139-142° C.; 1H NMR (400 MHz, CDCl3) δ 11.91 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 8.01-7.92 (m, 2H), 7.89-7.82 (m, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.49 (dddd, J=14.7, 8.1, 6.9, 1.5 Hz, 2H), 7.40 (dd, J=8.2, 7.0 Hz, 1H), 7.30 (dd, J=6.9, 1.2 Hz, 1H), 6.84 (d, J=5.2 Hz, 1H), 5.20-5.02 (m, 3H), 4.04 (dd, J=11.7, 7.3 Hz, 1H), 3.92 (s, 3H), 3.60 (d, J=4.1 Hz, 2H), 3.43 (dd, J=11.7, 7.1 Hz, 1H), 3.23 (dd, J=14.2, 3.2 Hz, 1H), 2.79-2.64 (m, 2H), 2.36-2.23 (m, 1H), 1.43-1.37 (m, 3H), 1.29 (dd, J=7.0, 3.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 176.37, 171.12, 168.88, 155.32, 148.71, 140.60, 134.68, 133.97, 131.94, 130.09, 128.97, 127.76, 127.35, 126.02, 125.57, 125.37, 123.45, 109.55, 76.95, 74.38, 72.09, 56.07, 51.42, 44.93, 34.37, 32.19, 19.14, 19.07, 18.26; HRMS-ESI (m/z) [M+H]+ calcd for C30H35N2O8 expected, 551.2388. found 551.2388.

Workup

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

Sources & evidence

ORD record
ord-3ce34c5564fb41b08af3cf5d76e1ed8c
Source dataset
uspto-grants-2016_09
Patent number
US09439422B2

Linked notes

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