Toluene → HCID 68427302, compound

HRID 2191309Notes

Reaction equation

HRID 2191309 reaction equation
[CH:1]1([OH:4])[CH2:3][CH2:2]1.[C:5]1(C)C=CC=C[CH:6]=1.[H-].[Na+].Cl[C:15]1[CH:16]=[CH:17][C:18]2[CH2:19][N:20](C(OC(C)(C)C)=O)[CH2:21][CH2:22][O:23][C:24]=2[N:25]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:1]1([O:4][C:15]2[CH:16]=[CH:17][C:18]3[CH2:19][NH:20][CH2:21][CH2:22][O:23][C:24]=3[N:25]=2)[CH2:6][CH2:5][CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 1140Toluene2×HCID 24758Sodium hydrideHCID 123361CyclopropanolHCID 634876Binap, (A+-)-HCID 57356939Tert-butyl 8-chloro-2,3-dihydropyrido[3,2-F][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 68427302HCID 68427302, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A solution of cyclopropanol in toluene (0.24 mol/L, 0.50 mL; 0.12 mmol) was placed in a reaction container, sodium hydride (0.008 g; 0.20 mmol) was added at room temperature, and the resulting mixture was stirred for 1 hr. A solution of tert-butyl 8-chloro-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.2 M) in toluene (0.50 mL; 0.10 mmol), BINAP (0.0022 g; 0.0036 mmol) and Pd2(dba)3 (0.0014 g; 0.0015 mmol) were added in this order, the reaction container was purged with argon and the resulting mixture was stirred at 100° C. for 24 hr with heating. The reaction mixture was cooled to room temperature, water (2 mL) was added, and the resulting mixture was extracted with ethyl acetate (3 mL). The ethyl acetate solvent was evaporated under reduced pressure, the residue was dissolved in DMSO (1 mL), and the solution was purified by preparative HPLC to give the title compound as an N-protected form. TFA (1.5 mL) was added to the protected form, and the resulting mixture was stirred at room temperature for 14 hr. TFA was evaporated under reduced pressure, and the residue was dissolved in water (1 mL). The solution was purified by high polar preparative HPLC to give the title compound as a TFA salt.

Workup

  1. additionwas added at room temperature
  2. customthe reaction container was purged with argon
  3. stirringthe resulting mixture was stirred at 100° C. for 24 hr
  4. temperaturewith heating
  5. additionwater (2 mL) was added
  6. extractionthe resulting mixture was extracted with ethyl acetate (3 mL)
  7. customThe ethyl acetate solvent was evaporated under reduced pressure
  8. dissolutionthe residue was dissolved in DMSO (1 mL)
  9. customthe solution was purified by preparative HPLC

Sources & evidence

ORD record
ord-d3677e5f34834ea590087b3c2009a61d
Source dataset
uspto-grants-2012_12
Patent number
US08329687B2

Reaction notes

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