Diethyl Ether → 4-isobutyloxybenzyl isocyanate

HRID 1453777Notes

Reaction equation

HRID 1453777 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12]C(O)=O)=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3].CN(C1C2C([N:29]([CH3:31])C)=CC=CC=2C=CC=1)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:39])C=CC=CC=1.C(OCC)C>C1COCC1>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][N:29]=[C:31]=[O:39])=[CH:10][CH:11]=1)[CH:2]([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 88675Proton spongeHCID 199401P,P-Diphenylphosphinic azideHCID 12199197[4-(2-Methylpropoxy)phenyl]acetic acid

Product 1

HCID 574300934-isobutyloxybenzyl isocyanate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-isobutoxyphenylacetic acid (7.6 g, 36.5 mmol) was dissolved in THF (50 mL). Proton Sponge™ (8.2 g, 38 mmol) was added, and the mixture was stirred for 15 min. Diphenylphosphoryl azide (10.6 g, 38 mmol) was added dropwise and the mixture was heated to reflux for 4 h. The mixture was cooled to room temperature and placed in the freezer at −18° C. for 20 h. The resulting white precipitate was vigorously stirred with diethyl ether (250 mL) for 15 min and filtered. The filtrate was evaporated to give crude 4-isobutoxybenzyl isocyanate (1.97 g, 9.6 mmol), which was dissolved in dichloromethane (50 mL) and added to a solution of 50ELH85 (2.91 g, 9.6 mmol) in dichloromethane (50 mL). The reaction mixture was stirred for 20 h and concentrated. The crude product was purified by flash chromatography (0-5% methanol in dichloromethane) to give N-(4-fluorobenzyl)-N-[1-(trifluoroacetyl)piperidin-4-yl]-N′-(4-isobutyloxybenzyl)carbamide (76ELH17, 3.90 g, 91%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 h
  3. waitplaced in the freezer at −18° C. for 20 h
  4. filtrationfiltered
  5. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-ae2c4ef49e264611bd3e4d9e903d88c5
Source dataset
uspto-grants-2009_01
Patent number
US07476682B2

Reaction notes

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