Hydrochloric Acid → 2-Chloro-5-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazole

HRID 46196Notes

Reaction equation

HRID 46196 reaction equation
[Cl:1][C:2]1[CH:14]=[CH:13][C:12]([C@H:15]2[C@H:20]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C@@H:19]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C@H:18]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C@@H:17]([CH2:45][O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[O:16]2)=[CH:11][C:3]=1[CH2:4][C:5]1[S:9][C:8](N)=[N:7][N:6]=1.N([O-])=O.[Na+].[ClH:58]>C(O)(=O)C.O.[Cu]>[Cl:58][C:8]1[S:9][C:5]([CH2:4][C:3]2[CH:11]=[C:12]([C@H:15]3[C@H:20]([O:21][CH2:22][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[C@@H:19]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C@H:18]([O:37][CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C@@H:17]([CH2:45][O:46][CH2:47][C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[O:16]3)[CH:13]=[CH:14][C:2]=2[Cl:1])=[N:6][N:7]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 672874215-(2-Chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 672869552-Chloro-5-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazoleYield 22%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 5-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-1,3,4-thiadiazol-2-amine (4.0 mmol) from Step 1 and copper (0.04 g, 0.62 mmol) in hydrochloric acid (37%, 6 mL) and acetic acid (30 mL) at 0° C. was slowly added sodium nitrite (2.8 g, 40 mmol) while maintaining an internal reaction temperature below 10° C. After 1 h stirring at 0° C., the resulting mixture was stirred with gradual warming to ambient temperature over 2 h. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and evaporated in vacuo. Flash chromatography on a Biotage® purification apparatus (silica gel, 10 to 60% ethyl acetate in hexanes) yielded the title compound (0.66 g, 0.86 mmol, 22%) as yellow oil.

Workup

  1. temperaturewhile maintaining an internal reaction temperature below 10° C
  2. stirringthe resulting mixture was stirred
  3. temperaturewith gradual warming to ambient temperature over 2 h
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customFlash chromatography on a Biotage® purification apparatus (silica gel, 10 to 60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d743dff8d20b4c7db093f3e66df255a1
Source dataset
uspto-grants-2013_09
Patent number
US08541380B2

Reaction notes

Loading…