Hydrochloric Acid → HCID 86584545, compound

HRID 1794715Notes

Reaction equation

HRID 1794715 reaction equation
B.C1COCC1.Br[CH2:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]([Cl:22])=[C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH:16]=1)=[O:10].Cl.[N-:24]=[N+:25]=[N-:26].[Na+].[I-].[Na+]>C1COCC1>[N:24]([CH2:8][C@@H:9]([C:11]1[CH:12]=[CH:13][C:14]([Cl:22])=[C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH:16]=1)[OH:10])=[N+:25]=[N-:26]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 33557Sodium AzideHCID 2723981Borane;tetrahydrofuranHCID 22141400HCID 22141400, compound

Product 1

HCID 86584545HCID 86584545, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

R-2-Methyl-CBS-oxazaborolidine (1.0 M in THF, 2 mL, 2 mmol) in 50 mL of THF was added slowly to a stirred solution of borane-THF complex (1.0 M in THF, 12 mL, 12 mmol) at room temperature. The mixture was stirred for 30 minutes and then N-(5-bromoacetyl-2-chloro-phenyl)-methanesulfonamide (which was obtained in Example 24) (2.80 g, 8.6 mmol) in 50 ml of THF was added dropwise. Upon stirring over night hydrochloride (1.0 M solution in diethyl ether) was added until the pH was ˜1. After stirring for one hour the reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried over MgSO4 and concentrated. The residue was then dissolved in 50 mL of DMSO. To the solution sodium azide (2.93 g, 45 mmol) and sodium iodide (3 g, 20 mmol) were added. After stirring at room temperature for 3 days the reaction was quenched with water, extracted with diethyl ether. The organic layer was dried over MgSO4 and concentrated. The product was purified by flash silica gel chromatography eluting with ethyl acetate and hexanes to give the title compound as a white solid (1.6 g, 64%); 1H NMR (300 MHz, CDCl3) δ 2.60(d, J=5.9 Hz, 1 H), 3.06(s, 3 H), 3.45–3.50(m, 2 H), 4.85–4.95(m, 1 H), 6.84(brs, 1 H), 7.22(dd, J=8.3, 2.0 Hz, 1 H), 7.44(d, J=8.3 Hz, 1 H), 7.65 (d, J=2.0 Hz, 1 H); MS (ES) m/z: 288.9 ((M−H)−, 100%); HRMS Calcd. for C9H12ClN4O3S(M+): 290.0241. Found: 290.0228.

Workup

  1. additionwas added until the pH was ˜1
  2. stirringAfter stirring for one hour the reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. dry with materialThe organic phase was dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was then dissolved in 50 mL of DMSO
  7. stirringAfter stirring at room temperature for 3 days the reaction
  8. customwas quenched with water
  9. extractionextracted with diethyl ether
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated
  12. customThe product was purified by flash silica gel chromatography
  13. washeluting with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-ff7cc35a705d4eb49f808ef01c42231c
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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