Benzyl Alcohol → HCID 118114472, compound

HRID 2284850Notes

Reaction equation

HRID 2284850 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:27]([CH2:30]C)CC.[CH2:32]([OH:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:47])C=CC=CC=1>O1CCOCC1>[CH2:32]([O:39][C:30]([NH:27][C:12]1[CH:11]=[C:10]([C@H:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[CH:18]=[CH:17][CH:16]=1)=[O:47])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 118114299HCID 118114299, compound

Product 1

HCID 118114472HCID 118114472, compoundYield 93.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-3-(((tert-butoxycarbonyl)amino)(phenyl)methyl)benzoic acid (100 mg, 0.31 mmol), Et3N (0.17 mL, 1.24 mmol) and benzyl alcohol (0.26 mL, 2.48 mmol) in dioxane (1.5 mL) was added diphenyl phosphoryl azide (93 mg, 0.34 mmol) at room temperature. The resulting mixture was heated to reflux for 24 h, cooled to room temperature and partitioned between EtOAc (30 mL) and water (20 mL). The layers were separated and the organic phase dried over MgSO4. The mixture was filtered and solvent was removed in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% EtOAc in isohexane, to give the corresponding compound tert-butyl N—[(S)-[3-(benzyloxycarbonylamino)phenyl]-phenyl-methyl]carbamate as a white solid (125 mg). To a solution of the solid (125 mg, 0.29 mg) in EtOAc (4 mL) was added 10% Pd/C (140 mg) and ammonium formate (200 mg, 3.07 mmol). The resulting slurry was refluxed for 2 h. The reaction mixture was then filtered over celite at room temperature, the cake washed with EtOAc (50 mL) and the filtrate concentrated in vacuo. The resulting oil solidified on standing to give the title compound (42 mg, 45% over two steps) as a white solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 24 h
  3. custompartitioned between EtOAc (30 mL) and water (20 mL)
  4. customThe layers were separated
  5. dry with materialthe organic phase dried over MgSO4
  6. filtrationThe mixture was filtered
  7. customsolvent was removed in vacuo
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 0-20% EtOAc in isohexane

Sources & evidence

ORD record
ord-53cccec28040422188240bbe722c71ed
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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