4-Methylmorpholine → HCID 86701276, compound

HRID 2276076Notes

Reaction equation

HRID 2276076 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:17][O:16][C:15](=[O:18])[C@H:14]([CH2:19]C(O)=O)[C@@H:13]([O:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[C@H:12]([CH3:29])[O:11][C:10]1=[O:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[SH:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][N+:48]=1[O-].[Al]>C1COCC1>[C:24]([O:23][C@@H:13]1[C@@H:14]([CH2:19][S:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[C:15](=[O:18])[O:16][CH2:17][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:10](=[O:30])[O:11][C@H:12]1[CH3:29])(=[O:28])[CH:25]([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 5359268AluminumHCID 86701256HCID 86701256, compoundHCID 178526253HCID 178526253, compound

Product 1

HCID 86701276HCID 86701276, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-((3S,7R,8R,9S)-3-(tert-butoxycarbonylamino)-8-(isobutyryloxy)-9-methyl-2,6-dioxo-1,5-dioxonan-7-yl)acetic acid (500 mg, 1.2 mmol) in anhydrous THF (7 mL) at −15° C. was added N-methylmorpholine (127 μL, 1.2 mmol) and isobutylchloroformate (152 μL, 1.2 mmol). The mixture was stirred for 5 min and then treated with a solution of 2-mercaptopyridine N-oxide (177 mg, 1.4 mmol) and TEA (162 μL, 1.2 mmol) in THF (2 mL). The reaction was stirred at −15° C. in the dark (covered with aluminum foil) for 1 h. The reaction was then filtered, concentrated, and the resulting bright yellow residue dissolved in CH2Cl2 (5 mL) and irradiated for 1 hr. The crude reaction mixture was concentrated and purified by flash chromatography (SiO2, 10% EtOAc/hexanes) to furnish the title compound (169 mg, 29%) as a fluffy white solid: mp 54-58° C.; IR (neat) 3370, 2980, 2939, 2878, 1753, 1718 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J=4.9 Hz, 1H), 7.48-7.41 (m, 1H), 7.11 (d, J=8.0 Hz, 1H), 7.00-6.94 (m, 1H), 5.32 (bs, J=12.9 Hz, 1H), 5.21-5.07 (m, 2H), 4.87 (dt, J=16.1, 6.4 Hz, 2H), 3.66-3.60 (m, 1H), 3.59 (bs, 1H), 3.15-3.00 (m, 2H), 2.68 (dq, J=14.2, 7.1 Hz, 1H), 1.43 (s, 9H), 1.33-1.25 (m, 9H); 13C NMR (101 MHz, CDCl3) δ 176.11, 171.91, 171.33, 157.67, 155.07, 149.73, 136.35, 122.89, 120.10, 81.00, 75.34, 74.76, 66.22, 51.66, 51.26, 34.68, 28.74, 28.64 (3), 19.38, 19.23, 18.14; ESIMS m/z 519 ([M+Na]+).

Workup

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. dissolutionthe resulting bright yellow residue dissolved in CH2Cl2 (5 mL)
  4. customirradiated for 1 hr
  5. customThe crude reaction mixture
  6. concentrationwas concentrated
  7. custompurified by flash chromatography (SiO2, 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ffa4ee5556e34d229471713aaecf7299
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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