Tetrahydrofuran → HCID 53776264, compound

HRID 1386796Notes

Reaction equation

HRID 1386796 reaction equation
CON(C)[C:4](=[O:20])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1.C1COCC1.[F:27][C:28]1[CH:33]=[CH:32][C:31]([Mg]Br)=[CH:30][CH:29]=1.[BH4-].[Na+]>CCOCC.CO>[F:27][C:28]1[CH:33]=[CH:32][C:31]([CH:4]([OH:20])[CH2:5][CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:11][CH2:12]2)=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 22458230HCID 22458230, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 53776264HCID 53776264, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 1.30 g (4.5 mmol) of N-methoxy-N-methyl-3-(1-(t-butoxycarbonyl)piperidin-4-yl)propionamide (from EXAMPLE 188, Step A) in 25 (of THF at 0° C. was treated with 3.0 mL of 2.0 M (4-fluoro)phenylmagnesium bromide in ether and stirred cold for 1 h. The reaction was quenched with 100 mL of 0.5 N HCl and extracted with 150 mL of ether. The extract was washed with 50 mL of sat'd NaCl, dried and concentrated. The crude ketone in 10 mL of MeOH at 0° C. was treated with 110 mg (2.2 mmol) of NaBH4 and the resulting mixture was stirred cold for 30 min. The reaction was quenched with 5 mL of 1.0 N NAOH. The quenched mixture was partitioned between 100 mL of ether and 25 m of H2O and the layers were separated. The organic layer was dried; the aqueous layer was extracted with 100 mL of ether, the extract dried and the organic layers combined and concentrated. Flash chromatography on 40 g of silica gel using 3:2 v/v hexanes/ether as the eluant afforded 566 mg (37%) of the title compound.

Workup

  1. customThe reaction was quenched with 100 mL of 0.5 N HCl
  2. extractionextracted with 150 mL of ether
  3. washThe extract was washed with 50 mL of sat'd NaCl
  4. customdried
  5. concentrationconcentrated
  6. stirringthe resulting mixture was stirred cold for 30 min
  7. customThe reaction was quenched with 5 mL of 1.0 N NAOH
  8. customThe quenched mixture was partitioned between 100 mL of ether and 25 m of H2O
  9. customthe layers were separated
  10. customThe organic layer was dried
  11. extractionthe aqueous layer was extracted with 100 mL of ether
  12. customthe extract dried
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-45e96ddd6f8b4ff887b6de5d84095904
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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