2-Methyltetrahydrofuran → HCID 67290121, compound

HRID 403414Notes

Reaction equation

HRID 403414 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.C(N(C(C)C)CC)(C)C.CC1CCCO1>CCOC(C)=O.CN1C(=O)CCC1>[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

7

Reactant 4

HCID 73012-MethyltetrahydrofuranHCID 769473-Methyl-5-isoxazolecarboxylic acidHCID 81531DiisopropylethylamineHCID 86664340HCID 86664340, compound

Product 1

HCID 67290121HCID 67290121, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
20 °C

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 (1.53 kg), 5-methylisoxazole-3-carboxylic acid (327 g), and NMP (4.74 kg) at 5° C. was added diisopropylethylamine (996 g). Propanephosphonic acid anhydride (817 g) was charged as a solution in EtOAc (817 g) and NMP (3.16 kg) to the reaction mixture. The reaction was allowed to proceed for 30 min at 5° C., then warmed to 20° C. and aged for an additional hour. The reaction solution was diluted with IPAc (10.5 kg) and 2-methyltetrahydrofuran (10.5 kg). The diluted reaction solution was washed with water (23.7 kg), a 1.0 M aqueous solution of H3PO4 (2×7.5 kg), water (7.9 kg), a 5% aqueous solution of NaHCO3 (7.5 kg), and then a 10% aqueous solution of NaCl (2×7.5 kg). The organic solution was concentrated under reduced pressure, diluted with THF (12 kg), and then filtered. Concentration of the organic solution to a volume of 5 L was followed by co-distillation with THF (30 kg) to a final volume of 5 L. The solution was diluted with THF (2.5 kg). The assay yield was determined on the product-containing solution to be 96.5% (1.35 kg).

Workup

  1. waitaged for an additional hour
  2. customThe diluted reaction solution
  3. washwas washed with water (23.7 kg)
  4. concentrationThe organic solution was concentrated under reduced pressure
  5. additiondiluted with THF (12 kg)
  6. filtrationfiltered
  7. additionThe solution was diluted with THF (2.5 kg)
  8. customThe assay yield

Sources & evidence

ORD record
ord-5111c35f742048ba92db02763cee86b8
Source dataset
uspto-grants-2014_06
Patent number
US08748374B2

Reaction notes

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