Acetyl chloride → HCID 56848036, compound

HRID 1038303Notes

Reaction equation

HRID 1038303 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](Cl)(=[O:41])[CH3:40]>N1C=CC=CC=1>[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:41])[CH3:40])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 56847989HCID 56847989, compound

Product 1

HCID 56848036HCID 56848036, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

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; 94.4 mg, 0.175 mmol) in pyridine (2 mL) was treated with acetyl chloride (70 μL, 0.98 mmol), and the mixture was allowed to stir at room temperature for 2.5 h. The mixture was then evaporated at room temperature under vacuum to a smaller volume. The concentrate was diluted with EtOAc and washed with 1 N HCl. The aqueous layer was extracted 3 times with EtOAc. The organic fractions were combined and dried with anhydrous MgSO4. The solvent was then evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 50% EtOAc in Hexane going to 90% EtOAc in Hexane in a single step). The title product (96.8 mg, 95%) was isolated as a colorless semi-solid: 1H NMR (300 MHz, CDCl3) δ 8.56 (s, 1H), 8.16 (d, J=8.4 Hz, 2H), 7.87-7.69 (m, 2H), 7.39 (d, J=8.1 Hz, 4H), 5.19 (dd, J=9.3, 6.6 Hz, 2H), 4.71 (d, J=16.1 Hz, 1H), 3.70-3.28 (m, 12H), 3.12 (dd, J=9.2, 7.9 Hz, 1H), 2.24 (s, 3H), 1.60 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 163.17, 141.89, 135.74, 129.76, 128.21, 126.89, 122.44, 121.26, 81.74, 79.82, 73.74, 69.61, 60.33, 58.86, 58.10, 21.05, 18.12; ESIMS m/z 581 (M+H).

Workup

  1. customThe mixture was then evaporated at room temperature under vacuum to a smaller volume
  2. additionThe concentrate was diluted with EtOAc
  3. washwashed with 1 N HCl
  4. extractionThe aqueous layer was extracted 3 times with EtOAc
  5. dry with materialdried with anhydrous MgSO4
  6. customThe solvent was then evaporated at room temperature under vacuum
  7. customThe resulting crude material was purified by silica gel chromatography (
  8. washeluting with 50% EtOAc in Hexane going to 90% EtOAc in Hexane in a single step)

Sources & evidence

ORD record
ord-8ca7a4ecdb1d48a79c6f732e38dbaca6
Source dataset
uspto-grants-2013_10
Patent number
US08551914B2

Reaction notes

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