Toluene → HCID 59190391, compound

HRID 219627Notes

Reaction equation

HRID 219627 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][CH2:11][CH2:12][CH2:13][C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:19])[CH2:15][C:16]([CH3:18])=[CH2:17])[CH3:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:33](Cl)(Cl)=[O:34].C1(C)C=CC=CC=1.[H-].[Na+]>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]2[CH2:11][CH2:12][CH2:13][C:14]([CH2:15][C:16]([CH3:18])=[CH2:17])([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[O:19][C:33]2=[O:34])[CH3:9])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 591903777-((1S)-1-(4-bromophenyl)ethylamino)-2-methyl-4-phenylhept-1-en-4-ol

Product 1

HCID 59190391HCID 59190391, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 7-((1S)-1-(4-bromophenyl)ethylamino)-2-methyl-4-phenylhept-1-en-4-ol (111.7 mg, 0.279 mmol) in anhydrous acetonitrile (7 mL) was cooled to 0° C. Triethylamine (78 μL, 2 equiv) and 20% phosgene in toluene solution (161 μL, 1.1 equiv) were added sequentially and slowly. After stirring 2 h at 0° C., NaH (60% in mineral oil, 22 mg, 2 equiv) was added. The mixture was stirred overnight and the ice bath was allowed to melt. LC-MS showed the reaction was complete. The mixture was cooled to 0° C. again, quenched by addition of satd aq NH4Cl (2 mL), concentrated to remove the organic solvents, diluted with ether (10 mL), washed with 1% HCl (3 mL), satd aq NaHCO3 (2 mL) and brine (2 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 12-g silica cartridge, eluted with a 15˜40% EtOAc in hexanes gradient, to afford 3-((1S)-1-(4-bromophenyl)ethyl)-7-(2-methylallyl)-7-phenyl-1,3-oxazepan-2-one (49.6 mg, 42%) as a mixture of two diastereomers.

Workup

  1. stirringThe mixture was stirred overnight
  2. temperatureThe mixture was cooled to 0° C. again
  3. customquenched by addition of satd aq NH4Cl (2 mL)
  4. concentrationconcentrated
  5. customto remove the organic solvents
  6. additiondiluted with ether (10 mL)
  7. washwashed with 1% HCl (3 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtration and concentration
  10. customthe residue was purified by chromatography on a 12-g silica cartridge
  11. washeluted with a 15˜40% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-fb3ccd0af2644cf5a4e5724e9d4be792
Source dataset
uspto-grants-2012_06
Patent number
US08202857B2

Reaction notes

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