Succinic anhydride → HCID 56848038, compound

HRID 1038305Notes

Reaction equation

HRID 1038305 reaction equation
[F:1][C:2]([F:38])([F:37])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:36]=[CH:35][C:18]([CH2:19][NH:20][O:21][C@H:22]4[C@H:27]([O:28][CH3:29])[C@H:26]([O:30][CH3:31])[C@@H:25]([O:32][CH3:33])[C@H:24]([CH3:34])[O:23]4)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[C:39]1(=[O:45])[O:44][C:42](=[O:43])[CH2:41][CH2:40]1>N1C=CC=CC=1.CCOC(C)=O>[F:38][C:2]([F:1])([F:37])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:36]=[CH:35][C:18]([CH2:19][N:20]([O:21][C@H:22]4[C@H:27]([O:28][CH3:29])[C@H:26]([O:30][CH3:31])[C@@H:25]([O:32][CH3:33])[C@H:24]([CH3:34])[O:23]4)[C:39](=[O:45])[CH2:40][CH2:41][C:42]([OH:44])=[O:43])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 7922Succinic anhydrideHCID 56847989HCID 56847989, compound

Product 1

HCID 56848038HCID 56848038, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzyl}-O-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-hydroxylamine (3; 140 mg, 0.26 mmol) in pyridine (5 mL) was added succinic anhydride (large excess), and the mixture stirred at room temperature for 3.5 h. The mixture was diluted with EtOAc and washed with 1 N HCl. The aqueous fraction was extracted with EtOAc (2×). The organic fractions were combined, washed with brine, dried with anhydrous MgSO4 and evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 80% EtOAc in Hexane going to 100% EtOAc over a short gradient). The title product (64 mg, 39%) was isolated as a white solid: mp 61-75° C.; 1H NMR (300 MHz, CDCl3) δ 8.63 (s, 1H), 8.16 (d, J=8.3 Hz, 2H), 7.93-7.68 (m, 2H), 7.40 (d, J=8.4 Hz, 4H), 5.40-5.10 (m, 2H), 4.76 (d, J=16.1 Hz, 1H), 3.73-3.25 (m, 13H), 3.15 (dd, J=9.1, 7.9 Hz, 1H), 3.04-2.60 (m, 4H), 1.27 (dd, J=9.8, 4.3 Hz, 3H); ESIMS m/z 639 (M+H), 638 (M+).

Workup

  1. washwashed with 1 N HCl
  2. extractionThe aqueous fraction was extracted with EtOAc (2×)
  3. washwashed with brine
  4. dry with materialdried with anhydrous MgSO4
  5. customevaporated at room temperature under vacuum
  6. customThe resulting crude material was purified by silica gel chromatography (
  7. washeluting with 80% EtOAc in Hexane going to 100% EtOAc over a short gradient)

Sources & evidence

ORD record
ord-b4ba315f7da84c479f27dbfb51265854
Source dataset
uspto-grants-2013_10
Patent number
US08551914B2

Reaction notes

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