tert-Butanol → [1-(4-Bromo-3-fluoro-phenyl)-cyclopropyl]-carbamic acid tert-butyl ester

HRID 1874090Notes

Reaction equation

HRID 1874090 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(C(O)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[F:14].CC[N:17]([CH:21](C)C)C(C)C.[C:24]([OH:28])([CH3:27])([CH3:26])[CH3:25].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:36])C=CC=CC=1>C1(C)C=CC=CC=1>[C:24]([O:28][C:21](=[O:36])[NH:17][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([F:14])[CH:4]=2)[CH2:9][CH2:10]1)([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 116518041-(4-Bromo-3-fluorophenyl)cyclopropane-1-carboxylic acid

Product 1

HCID 67159700[1-(4-Bromo-3-fluoro-phenyl)-cyclopropyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1-(4-bromo-3-fluorophenyl)cyclopropanecarboxylic acid (7.4 g, 28.6 mmol, prepared from 1-bromo-4-bromomethyl-2-fluorobenzene according to Peretto et al. J Med. Chem. 2005, 48, 5705-20), DIPEA (6.36 mL, 37.1 mmol), tert-butanol (67.0 mL, 714 mmol), diphenylphosphorylazide (7.37 mL, 34.3 mmol) and molsieve (4 Å) in 100 mL toluene is stirred under reflux overnight. The reaction mixture is filtered and concentrated in vacuo. The residue is taken up in ethylacetate and washed with 5% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and brine. The organic phase is dried over MgSO4 and concentrated in vacuo. Yield: 9.37 g.

Workup

  1. temperatureunder reflux overnight
  2. filtrationThe reaction mixture is filtered
  3. concentrationconcentrated in vacuo
  4. washwashed with 5% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and brine
  5. dry with materialThe organic phase is dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a125cf88e5744c99318cccd84039af9
Source dataset
uspto-grants-2012_11
Patent number
US08304556B2

Reaction notes

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