Triphenylphosphine → (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

HRID 470171

Reaction equation

HRID 470171 reaction equation
[F:1][C:2]1[C:7]2[N:8]=[CH:9][NH:10][C:6]=2[C:5]([F:11])=[CH:4][N:3]=1.[H-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([O:36][C@H:37]1[CH:41]=[CH:40][C@@H:39](O)[CH2:38]1)=O>CN(C=O)C.C1COCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([C@@H:40]3[CH2:41][C@H:37]([OH:36])[CH:38]=[CH:39]3)[C:6]=2[C:5]([F:11])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 178506010HCID 178506010, compound

Product 1

HCID 58329283(1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (2.0 g, 12.9 mmol, 1 equiv) was dissolved in dry DMF (21 mL). Sodium hydride (542 mg, 13.5 mmol, 1.05 equiv) was carefully added. The resulting mixture was stirred at ambient temperature for 45 minutes at which point triphenylphosphine (507 mg, 1.9 mmol, 0.15 equiv), Pd-tetrakis (745 mg, 0.6 mmol, 0.05 equiv) and (1R,3S)-(+)-cis-4-cyclopentene-1,3-diol 1-acetate (3-1) (2.2 g, 15.5 mmol, 1.2 equiv) in dry THF (21 mL) were added. The mixture was stirred at 60° C. for 16 hours, then cooled to ambient temperature, diluted with 100 mL EtOAc and washed with 50 mL water. The aqueous layer was washed with EtOAc three additional times, and the combined washings were dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier) to afford (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (3-2) as a white solid. LRMS m/z (M+H) 238.0 found, 238.1 required.

Workup

  1. additionwere added
  2. temperaturecooled to ambient temperature
  3. washwashed with 50 mL water
  4. washThe aqueous layer was washed with EtOAc three additional times
  5. dry with materialthe combined washings were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-99a7170ad43d48d4bcf9588f4f702bd6
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Linked notes

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