Chloroform → HCID 15056965, compound

HRID 359565Notes

Reaction equation

HRID 359565 reaction equation
[CH3:1][C:2]1([CH3:20])[CH2:7][CH2:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([CH3:15])[CH:9]=2)[CH:3]1[C:16]([O:18][CH3:19])=[O:17].[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C(Cl)(Cl)Cl.[BH3-]C#N.[Na+]>Cl.CO>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:4]2[CH:3]([C:16]([O:18][CH3:19])=[O:17])[C:2]([CH3:20])([CH3:1])[CH2:7][CH:6]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:5]=2)=[CH:9][C:10]=1[CH3:15]

Participants

7

Reactant 4

HCID 6212ChloroformHCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 15125260HCID 15125260, compound

Product 1

HCID 15056965HCID 15056965, compoundYield 66.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolvent2×

Procedure

A solution of 4a (11.05 g, 38.1 mmol) and pyrrolidine (8.13 g, 0.114 mol) in 11.5 mL of 5N HCl in methanol (57.1 mmol) and 100 mL chloroform was stirred at ambient temperature overnight and the volatiles were removed in vacuo. The residue was dissolved in 100 mL methanol and 5N HCl methanol was added until the mixture became acidic (bromocresol green). To the solution was added NaCNBH3 (2.40 g, 38.7 mmol) and the reaction was maintained at pH 3-5 by the dropwise addition of 5N HCl in methanol. After stirring overnight the volatiles were removed in vacuo. The residue was diluted with ether and 1N NaOH. The organic layer was washed with H2O and brine and dried (MgSO4). Removal of the volatiles in vacuo and purification of the residue by HPLC using 1% Et3N in 1:1 hexanes:EtOAc as the eluent provided 8.75 g of the oily product.

Workup

  1. customthe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in 100 mL methanol
  3. addition5N HCl methanol was added until the mixture
  4. customwere removed in vacuo
  5. additionThe residue was diluted with ether and 1N NaOH
  6. washThe organic layer was washed with H2O and brine
  7. dry with materialdried (MgSO4)
  8. customRemoval of the volatiles
  9. customin vacuo and purification of the residue by HPLC

Sources & evidence

ORD record
ord-4c00fdb4f43b4a7fb39bb56e4d1403f1
Source dataset
uspto-grants-1991_03
Patent number
US05001144

Reaction notes

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