Pyridine → HCID 86701267, compound

HRID 2276068Notes

Reaction equation

HRID 2276068 reaction equation
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17][OH:18])[C:14](=[O:19])[O:13][CH2:12][C@H:11]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:10](=[O:28])[O:9][C@H:8]1[CH3:29])(=[O:5])[CH:2]([CH3:4])[CH3:3].N1C=CC=CC=1.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C(Cl)Cl>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17][O:18][S:37]([CH3:36])(=[O:39])=[O:38])[C:14](=[O:19])[O:13][CH2:12][C@H:11]([NH:20][C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[C:10](=[O:28])[O:9][C@H:8]1[CH3:29])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 86701260HCID 86701260, compound

Product 1

HCID 86701267HCID 86701267, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

To a solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(2-hydroxyethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (660 mg, 1.58 mmol) in CH2Cl2 (15 mL) at 0° C. was added pyridine (750 mg, 9.48 mmol), followed by methanesulfonyl chloride (362 mg, 3.16 mmol). The resulting reaction mixture was warmed up to room temperature (about 22° C.) and stirred overnight. The reaction mixture was partitioned between sat'd aqueous NaHCO3 solution (30 mL) and EtOAc (40 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×30 mL) and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (660 mg, 84%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 5.06 (t, J=9.8 Hz, 1H), 4.95-4.77 (m, 2H), 4.32-4.19 (m, 1H), 4.13-4.05 (m, 1H), 3.62 (s, 1H), 2.98 (s, 3H), 2.78 (dd, J=14.9, 6.4 Hz, 1H), 2.62 (dt, J=13.9, 7.0 Hz, 1H), 2.25-2.08 (m, 1H), 1.83 (s, 1H), 1.47 (d, J=11.9 Hz, 9H), 1.28 (d, J=6.3 Hz, 3H), 1.21 (d, J=6.9 Hz, 6H); ESIMS m/z 496 ([M+H]+).

Workup

  1. customThe resulting reaction mixture
  2. customThe reaction mixture was partitioned between sat'd aqueous NaHCO3 solution (30 mL) and EtOAc (40 mL)
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with additional EtOAc (2×30 mL)
  5. dry with materialthe combined EtOAc extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-cc02c69e0d044141aa114574685affb0
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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