Tributylphosphine → HCID 72319396, compound

HRID 1922173Notes

Reaction equation

HRID 1922173 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([CH:13]([OH:18])[CH2:14][CH:15]([CH3:17])[CH3:16])[C:9]1=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:20][C:21]1[CH:26]=[CH:25][C:24](O)=[CH:23][N:22]=1.C(P(CCCC)CCCC)CCC.C1CCN(C(/N=N/C(N2CCCCC2)=O)=O)CC1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([CH:13]([O:18][C:24]2[CH:23]=[N:22][C:21]([Cl:20])=[CH:26][CH:25]=2)[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 13831Tributylphosphine2×HCID 516892Sodium BicarbonateHCID 8198212-Chloro-5-hydroxypyridineHCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)2×HCID 67492993HCID 67492993, compound2×

Product 1

HCID 72319396HCID 72319396, compoundYield 20.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Bubble nitrogen through a solution of 3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (D1) (600 mg, 2.33 mmol) and 2-chloro-5-hydroxy-pyridine (0.451 g, 3.50 mmol) in toluene (10 mL) at room temperature for 10 minutes. Add tri-n-butylphosphine (0.872 mL, 3.50 mmol) followed by azodicarboxylic acid dipiperidide (0.882 g, 3.50 mmol). Heat the reaction mixture to 70° C., and stir over night. Add additional 3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (D1) (600 mg, 2.33 mmol), tri-n-butylphosphine (0.872 mL, 3.50 mmol) and azodicarboxylic acid dipiperidide (0.882 g, 3.50 mmol). Continue to stir at 70° C. for 3 hours. Cool the mixture to room temperature and pour into saturated aqueous NaHCO3. Extract with ethyl acetate (2×), combine the organic extracts, dry (Na2SO4), filter and concentrate. Purify the crude residue by silica gel chromatography eluting with 0-20% ethyl acetate in hexanes to afford 180 mg of 3-[1-(6-chloro-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (D2) for chiral separation.

Workup

  1. stirringContinue to stir at 70° C. for 3 hours
  2. temperatureCool the mixture to room temperature
  3. extractionExtract with ethyl acetate (2×)
  4. dry with materialdry (Na2SO4)
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude residue by silica gel chromatography
  8. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-03464dd6cb214d3dacbf78642c484687
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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