Hydrochloric Acid → HCID 58204818, compound

HRID 886099Notes

Reaction equation

HRID 886099 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:7]([CH:11]=[C:12](I)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2[C:37]3[O:36]C4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C[OH:60].C(N(CC)CC)C.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:37]([OH:36])=[O:60])[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58204465HCID 58204465, compound

Product 1

HCID 58204818HCID 58204818, compoundYield 648%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
50 °C

Procedure

A round bottom flask containing 9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazapine (0.794 g, 2.40 mmol) was purged thoroughly with nitrogen. Palladium (II) acetate (27 mg, 0.12 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (139 mg, 0.24 mmol) was added sequentially with more purging. Methanol (10 mL, 200 mmol) and triethylamine (30 mL, 200 mmol) purged with nitrogen were added and the reaction mixture was purged with Carbon monoxide for 5 minutes. Two Carbon monoxide balloons were attached and the reaction mixture was heated at 50° C. for 4.5 hours. Complete formation of the methyl ester was confirmed by LCMS. Purged reaction with nitrogen and concentrated in vacuo. Purified the ester by flash chromatography on the ISCO 0 to 50% ethyl acetate in heptane and concentrated in vacuo. The ester was dissolved in tetrahydrofuran and (20 mL, 200 mmol) and 1 M Lithium hydroxide was added (7.22 mL) and the reaction was stirred for three days. Complete hydrolysis by LCMS. Adjusted to pH ˜5 with 1 M HCl and extracted off the product with dichloromethane and 5% methanol to give 9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylic acid (0.386 g, 64.6% yield)

Workup

  1. customwas purged thoroughly with nitrogen
  2. customwith more purging
  3. additionwere added
  4. customthe reaction mixture was purged with Carbon monoxide for 5 minutes
  5. customPurged
  6. customreaction with nitrogen
  7. concentrationconcentrated in vacuo
  8. customPurified the ester by flash chromatography on the ISCO 0 to 50% ethyl acetate in heptane
  9. concentrationconcentrated in vacuo
  10. dissolutionThe ester was dissolved in tetrahydrofuran
  11. addition(20 mL, 200 mmol) and 1 M Lithium hydroxide was added (7.22 mL)
  12. customComplete hydrolysis by LCMS
  13. extractionextracted off the product with dichloromethane and 5% methanol

Sources & evidence

ORD record
ord-e40d50e17132468eae7c4dbaae4d2d0f
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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