Pyridine → HCID 58577920, compound

HRID 473963Notes

Reaction equation

HRID 473963 reaction equation
[CH2:1]([CH:3]1[O:8][C:7]2[CH:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])=[N:17][CH:18]=3)[CH:11]=[CH:12][C:6]=2[NH:5][CH2:4]1)[CH3:2].N1C=CC=CC=1.[Cl:34][C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Cl:34][C:35]([N:5]1[CH2:4][CH:3]([CH2:1][CH3:2])[O:8][C:7]2[CH:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][C:21]([CH3:26])([CH3:27])[C:22]([O:24][CH3:25])=[O:23])=[N:17][CH:18]=3)[CH:11]=[CH:12][C:6]1=2)=[O:37]

Participants

5

Reactant 3

HCID 1049PyridineHCID 94429TriphosgeneHCID 58577961HCID 58577961, compound

Product 1

HCID 58577920HCID 58577920, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of methyl 3-(5-(2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-10 (248.0 mg, 0.60 mmol) and dry pyridine (97.0 μL, 1.20 mmol) in anhydrous methylene chloride (3.0 mL) was added dropwise to a solution of triphosgene (71.2 mg, 0.24 mmol) in anhydrous methylene chloride (3.0 mL) at −20° C. under an atmosphere of argon. The reaction mixture was allowed to warm to room temperature over 30 mins and was stirred for 3 h at room temperature. It was then successively diluted with methylene chloride (25 mL), quenched with a 1 N aqueous solution of hydrogen chloride (1.0 mL), diluted with water (10 mL) and decanted. The aqueous layer was extracted with methylene chloride (3×30 mL); the combined extracts were washed with a 1 N aqueous solution of hydrogen chloride (20 mL), brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The light pink solid methyl 3-(5-(4-(chlorocarbonyl)-2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-11 (265.0 mg, Yield=100%) was used for the next step without purification and stored at −20° C. under an atmosphere of nitrogen. MS (ESI) [M+1]+ 433.

Workup

  1. customquenched with a 1 N aqueous solution of hydrogen chloride (1.0 mL)
  2. additiondiluted with water (10 mL)
  3. customdecanted
  4. extractionThe aqueous layer was extracted with methylene chloride (3×30 mL)
  5. washthe combined extracts were washed with a 1 N aqueous solution of hydrogen chloride (20 mL), brine (20 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe light pink solid methyl 3-(5-(4-(chlorocarbonyl)-2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-11 (265.0 mg, Yield=100%) was used for the next step without purification
  10. customstored at −20° C. under an atmosphere of nitrogen

Sources & evidence

ORD record
ord-776e0cd33417430b949b6e2a6ed3c841
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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