N-methyl-2-pyrrolidone → HCID 67290121, compound

HRID 403424Notes

Reaction equation

HRID 403424 reaction equation
CC1C=CC(S([O-])(=O)=O)=CC=1.[CH2:12]([O:14][C:15]([C@@:17]12[CH2:32][C@H:31]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]([NH3+:33])[C:22](=[O:34])[N:21]1[CH2:35][C@H:36]([O:38][C:39](=[O:49])[C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)[CH2:37][C@H:20]1[C:19](=[O:50])[NH:18]2)=[O:16])[CH3:13].[CH3:51][C:52]1[O:56][N:55]=[C:54]([C:57](O)=[O:58])[CH:53]=1.CN1C(=O)CCC1.C(N(C(C)C)CC)(C)C>CCOC(C)=O>[CH3:51][C:52]1[O:56][N:55]=[C:54]([C:57]([NH:33][C@@H:23]2[C:22](=[O:34])[N:21]3[CH2:35][C@H:36]([O:38][C:39](=[O:49])[C:40]4[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=4)[CH2:37][C@H:20]3[C:19](=[O:50])[NH:18][C@:17]3([C:15]([O:14][CH2:12][CH3:13])=[O:16])[CH2:32][C@H:31]3[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:58])[CH:53]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×HCID 769473-Methyl-5-isoxazolecarboxylic acidHCID 81531DiisopropylethylamineHCID 86664340HCID 86664340, compound

Product 1

HCID 67290121HCID 67290121, compoundYield 93.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R,6S,13aS,14aR,16aS,Z)-14a-(ethoxycarbonyl)-2-(4-nitrobenzoyloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-aminium 4-methylbenzenesulfonate (9.95 g), 5-methylisoxazole-3-carboxylic acid (2.12 g), and NMP (30.0 g) at 5° C. was added diisopropylethylamine (6.5 g). Propanephosphonic acid anhydride (5.3 g) was charged as a solution in EtOAc (5.3 g) and NMP (10 mL) to the reaction mixture. The reaction was warmed to rt over 14 h. The reaction solution was diluted with 2-Me-THF (150 mL). The diluted reaction solution was washed with water (150 mL), a 1.0 M aqueous solution of H3PO4 (2×50 mL), water (50 mL), a 5% aqueous solution of NaHCO3 (50 mL), and then a 10% aqueous solution of NaCl (2×50 mL). The organic solution was dried over MgSO4, filtered, and then concentrated under reduced pressure, and then co-distilled with THF (200 mL). THF was added and the product-containing solution was filtered and evaporated to an oil (8.5 g, 93% yield).

Workup

  1. customThe diluted reaction solution
  2. washwas washed with water (150 mL)
  3. dry with materialThe organic solution was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. additionTHF was added
  7. filtrationthe product-containing solution was filtered

Sources & evidence

ORD record
ord-cd6f000233bb4ce09e0dd242d452748c
Source dataset
uspto-grants-2014_06
Patent number
US08748374B2

Reaction notes

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