Ammonium Chloride → N-[2-(3-cyclopropyl-1-hydroxycyclobutyl)-phenyl]Formamide

HRID 2240482Notes

Reaction equation

HRID 2240482 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]=[O:10].C([Li])CCC.[CH:16]1([CH:19]2[CH2:22][C:21](=[O:23])[CH2:20]2)[CH2:18][CH2:17]1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH:16]1([CH:19]2[CH2:22][C:21]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[NH:8][CH:9]=[O:10])([OH:23])[CH2:20]2)[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 8179142-BromoformanilideHCID 128200383-Cyclopropylcyclobutan-1-oneHCID 178418339Butyllithium

Product 1

HCID 86761115N-[2-(3-cyclopropyl-1-hydroxycyclobutyl)-phenyl]Formamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-100 °C

Procedure

In a sulfonation flask, 7.8 g (0.039 mol) N-(2-bromophenyl)form amide was dissolved in a mixture of 100 ml dry tetrahydrofuran. The solution was cooled to −100° C. and 60 ml (0.096 mol) of n-butyllithium solution (1.6M in hexane) was added over a period of 1 hour in such at manner that the internal temperature remained constant at −100° C. (±2° C.). After stirring for 2.5 hours at −100° to −110° C., 5.3 g (0.048 mmol) of 3-cyclopropylcyclobutan-1-one (prepared as described in Example 7), dissolved in 30 ml of dry tetrahydrofuran, were added over a period of 30 minutes in such a manner that the internal temperature remained constant at −100° C. (±2° C.). After stirring for 3 hours at −78° C., the temperature was elevated to 0° C. in ca. 30 minutes. Concentrated ammonium chloride solution and ethyl acetate were added and the organic phase was washed several times with water. After drying and evaporation of the solvent in a water jet vacuum, the crude material was obtained. Purification was achieved by flash chromatography over silica gel (eluant: hexane/ethyl acetate 1:1). Yield: 2.55 g (23% of theory) of N-[2-(3-cyclopropyl-1-hydroxycyclobutyl)-phenyl]formamide in the form of a resin.

Workup

  1. customremained constant at −100° C.
  2. custom(±2° C.)
  3. additionwere added over a period of 30 minutes in such a manner that the internal temperature
  4. customremained constant at −100° C.
  5. custom(±2° C.)
  6. stirringAfter stirring for 3 hours at −78° C.
  7. waitthe temperature was elevated to 0° C. in ca. 30 minutes
  8. washthe organic phase was washed several times with water
  9. customAfter drying
  10. customevaporation of the solvent in a water jet vacuum

Sources & evidence

ORD record
ord-5967cfd9509d492483187b599a32a49a
Source dataset
uspto-grants-2010_05
Patent number
US07723371B2

Reaction notes

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