4-Methylmorpholine → [(S)-1-(7-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester

HRID 242785Notes

Reaction equation

HRID 242785 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:13])[C:10](O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[C:16]=1[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10]1[N:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:16]2[C:15]([F:14])=[CH:20][CH:19]=[CH:18][C:17]=2[N:21]=1)[CH3:13])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 692512983-Fluoro-N2-phenylbenzene-1,2-diamine

Product 1

HCID 68157602[(S)-1-(7-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl esterYield 77.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-2-tertbutoxycarbonylaminopropionic acid (480 mg, 2.53 mmol), 3-fluoro-N2-phenylbenzene-1,2-diamine (466 mg, 2.30 mmol), HOAt (345 mg, 2.53 mmol), 4-methylmorpholine (560 μL, 5.07 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (486 mg, 2.53 mmol) in DCM (15 mL) was stirred at RT for 2 h. The reaction mixture was then partitioned between additional DCM and an aqueous solution of NaHCO3. The organic layer was dried and concentrated in vacuo and the resulting residue (1.0 g) was dissolved in AcOH (20 mL) and stirred for 18 h at 70° C. After cooling to RT, volatiles were evaporated under reduced pressure and the residue was partitioned between EtOAc and a saturated solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) affording [(S)-1-(7-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester as a yellow/orange oil (631 mg, 77%). LCMS: RT 3.64 min [M+H]+ 356.0.

Workup

  1. customThe reaction mixture was then partitioned between additional DCM
  2. customThe organic layer was dried
  3. concentrationconcentrated in vacuo
  4. dissolutionthe resulting residue (1.0 g) was dissolved in AcOH (20 mL)
  5. stirringstirred for 18 h at 70° C
  6. temperatureAfter cooling to RT
  7. customvolatiles were evaporated under reduced pressure
  8. customthe residue was partitioned between EtOAc
  9. washThe organic layer was washed with water
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM)

Sources & evidence

ORD record
ord-33fcc3db74e44c5aabd66c296fb1666c
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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