Sodium Carbonate → N-cyclopropyl-3-(4,4-diethoxybutyl)-4-fluorobenzamide

HRID 1985756

Reaction equation

HRID 1985756 reaction equation
[CH2:1]([O:3][CH:4]([O:8][CH2:9][CH3:10])[CH2:5][CH:6]=[CH2:7])[CH3:2].B1C2CCCC1CCC2.C([O-])([O-])=O.[Na+].[Na+].Br[C:27]1[CH:28]=[C:29]([CH:36]=[CH:37][C:38]=1[F:39])[C:30]([NH:32][CH:33]1[CH2:35][CH2:34]1)=[O:31]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.C1C=CC=CC=1>[CH:33]1([NH:32][C:30](=[O:31])[C:29]2[CH:36]=[CH:37][C:38]([F:39])=[C:27]([CH2:7][CH2:6][CH2:5][CH:4]([O:8][CH2:9][CH3:10])[O:3][CH2:1][CH3:2])[CH:28]=2)[CH2:34][CH2:35]1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 2564264,4-Diethoxybut-1-eneHCID 220190903-Bromo-N-cyclopropyl-4-fluorobenzamide

Product 1

HCID 22019163N-cyclopropyl-3-(4,4-diethoxybutyl)-4-fluorobenzamideYield 93.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-butenal diethyl acetal (144 mg, 1 mmol) and 9-BBN (0.5 M in THF, 2.2 mL, 1.1 mmol) was stirred at RT for 1 h. The mixture was concentrated and to the residue were added benzene (2 mL), EtOH (1 mL), aqueous Na2CO3 solution (2M, 1 mL), 3-bromo-4-fluoro-N-cyclopropylbenzamide (127 mg, 0.5 mmol) and Pd(Ph3P)4 (40 mg). The resulting mixture was stirred at 80° C. for 2 h. The mixture was then cooled to RT and diluted with ethyl acetate (10 mL) and washed with water. The organic layer was separated and concentrated. The residue was purified by column chromatography (SiO2; EtOAc/hexane 1:3) to afford N-cyclopropyl-3-(4,4-diethoxybutyl)-4-fluorobenzamide (151 mg, 93%). This material was dissolved in acetone (1 mL) and 3 N HCl solution (0.2 mL) and stirred at RT for 1 h. The mixture was neutralized with NaHCO3 solution and extracted with ethyl acetate (3×5 mL). The organic layer was dried and concentrated to afford N-cyclopropyl-4-fluoro-3-(4-oxo-butyl)-benzamide (110 mg, 94%). 1H NMR (CDCl3) δ 9.76 (s, 1H), 7.63 (dd, 1H, J=7.5 and 2.2 Hz,), 7.58 (m, 1H), 7.03 (t, 1H, J=9.0 Hz,), 6.47 (s, NH, 1H), 2.87 (m, 1H), 2.69 (t, 2H, J=7.5 Hz,), 2.48 (m, 2H), 1.95 (m, 2H), 0.86 (m, 2H) and 0.62 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated and to the residue
  2. temperatureThe mixture was then cooled to RT
  3. washwashed with water
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (SiO2; EtOAc/hexane 1:3)

Sources & evidence

ORD record
ord-6acb1d04a85546bfb4027103cf1e03b9
Source dataset
uspto-grants-2009_06
Patent number
US07547711B2

Linked notes

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