Dichloromethane → HCID 71476292, compound

HRID 929904Notes

Reaction equation

HRID 929904 reaction equation
C([O:5][C:6]([C@:8]1([NH:27]C(OC(C)(C)C)=O)[CH2:13][C@@H:12]([S:14][C:15]2[CH:19]=[N:18][NH:17][N:16]=2)[C@@H:11]2[C@H:9]1[C@H:10]2[C:20]([O:22]C(C)(C)C)=[O:21])=[O:7])(C)(C)C.[Cl:35]CCl>[Br-].[Br-].[Zn+2]>[ClH:35].[NH2:27][C@@:8]1([C:6]([OH:7])=[O:5])[CH2:13][C@@H:12]([S:14][C:15]2[CH:19]=[N:18][NH:17][N:16]=2)[C@@H:11]2[C@H:9]1[C@H:10]2[C:20]([OH:22])=[O:21]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 86716593HCID 86716593, compound

Product 1

HCID 71476292HCID 71476292, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 10421208Zinc bromideCatalyst2×

Conditions

Temperature
50 °C

Procedure

Add zinc dibromide (0.88 g, 3.91 mmol) to a stirring solution of ditert-butyl(1R,2S,4R,5R,6R)-2-tert-butoxycarbonylamino-4-(2H-[1,2,3]triazol-4-ylsulfanyl)-bicyclo[3.1.0]hexane-2,6-dicarboxylate (194 mg, 0.39 mmol) in dichloromethane (30 mL). Stir overnight at 50° C. Add more zinc dibromide (0.44 g, 1.95 mmol) and continue to stir at 50° C. until starting material is completely consumed. Evaporate solvent and stir residue in 2M aqueous hydrochloric acid (5 mL) at 50° C. until only desired product is present. Cool reaction mixture and purify the residue by cation-exchange chromatography (DOWEX® 50WX8-100). Allow the compound to flow through the column at a drip rate of about 1 drop every 1-2 seconds. After the initial loading volume has dropped to the resin surface, rinse with water (5 to 10 mL) and repeat 3 times. Monitor the pH of the effluent and continue rinsing with water until application complete (pH cycle observed: effluent from the column initially at pH=7 then drop to pH=1 and return back to pH=7). Wash the column with at least one column volume each of water, water:tetrahydrofuran (1:1) then water. Displace the product from the resin with 10% pyridine:water. Continue to elute with 10% pyridine:water until no additional product is detected. Concentrate the fractions containing the product to obtain a colorless solid. Dry the solid. Dissolve in 2M hydrochloric acid and evaporate to provide the title compound as a white solid (94 mg, 75%). MS (m/z): 285 (M+1).

Workup

  1. stirringto stir at 50° C.
  2. customis completely consumed
  3. stirringEvaporate solvent and stir residue in 2M aqueous hydrochloric acid (5 mL) at 50° C. until only desired product
  4. temperatureCool
  5. customreaction mixture
  6. custompurify the residue by cation-exchange chromatography (DOWEX® 50WX8-100)
  7. customto flow through the column at a drip rate of about 1 drop every 1-2 seconds
  8. additionAfter the initial loading volume has dropped to the resin surface
  9. washrinse with water (5 to 10 mL) and repeat 3 times
  10. washMonitor the pH of the effluent and continue rinsing with water until application complete (pH cycle
  11. washWash the column with at least one column volume each of water, water:tetrahydrofuran (1:1)
  12. washto elute with 10% pyridine
  13. concentrationConcentrate the fractions
  14. additioncontaining the product
  15. customto obtain a colorless solid
  16. customDry the solid
  17. dissolutionDissolve in 2M hydrochloric acid
  18. customevaporate

Sources & evidence

ORD record
ord-07112105f9a1477ab568795b0126c51c
Source dataset
uspto-grants-2016_03
Patent number
US09296710B2

Reaction notes

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