Toluene → HCID 68770390, compound

HRID 2265230Notes

Reaction equation

HRID 2265230 reaction equation
[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][C@@H:7]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C@@H:8]([CH3:12])C(O)=O)([CH3:4])([CH3:3])[CH3:2].CC[N:24](CC)CC.Cl[C:30]([O:32]CC)=[O:31].[N-]=[N+]=[N-].[Na+].[C:39]1([CH3:45])[CH:44]=CC=C[CH:40]=1>C1COCC1.O.C(O)(C)(C)C>[C:39]([O:32][C:30](=[O:31])[NH:24][C@H:8]([CH3:12])[C@@H:7]([O:6][Si:5]([C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:20])[CH3:21])[C:13]1[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=1)([CH3:45])([CH3:44])[CH3:40]

Participants

9

Reactant 5

HCID 1140TolueneHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 68770353HCID 68770353, compound

Product 1

HCID 68770390HCID 68770390, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2R,3R)-3-(tert-butyl-dimethyl-silyloxy)-3-(4-chloro-phenyl)-2-methyl-propionic acid (0.93 g, 2.8 mmol) in THF (30 mL) at 0° C. was added Et3N (0.438 mL, 3.1 mmol) followed by ethyl chloroformate (0.30 mL, 3.1 mmol). The solution was stirred for 1 h at 0° C., and a solution of NaN3 (552 mg, 8.5 mmol) in water (10 mL) was added. The reaction solution was stirred for 4 h with warming to rt. The mixture was poured into water and extracted with Et2O (3×). The combined organic extracts were dried (MgSO4) and concentrated to afford the crude acyl azide. A mixture of the acyl azide, tert-butanol (10 mL), and toluene (20 mL) was heated at reflux for 12 h. The reaction mixture was cooled and concentrated, and the residue was purified by flash chromatography (EtOAc/hexanes) to provide the desired product as a colorless oil (354 mg, 31%). 1H NMR (400 MHz, CDCl3): 7.28 (s, 4H), 4.90 (br s, 1H), 4.60 (br d, J=8.0, 1H), 3.77-3.65 (m, 1H), 1.46 (s, 9H), 0.94 (s, 9H), 0.88 (d, J=6.8, 3H), 0.06 (s, 3H), −0.13 (s, 3H).

Workup

  1. stirringThe reaction solution was stirred for 4 h
  2. temperaturewith warming to rt
  3. extractionextracted with Et2O (3×)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customto afford the crude acyl azide
  7. temperaturewas heated
  8. temperatureat reflux for 12 h
  9. temperatureThe reaction mixture was cooled
  10. concentrationconcentrated
  11. customthe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-eeaefcda28d8440ca5660979cf097a91
Source dataset
uspto-grants-2010_12
Patent number
US07855292B2

Reaction notes

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