Ethyl diazoacetate → HCID 22111159, compound

HRID 565422Notes

Reaction equation

HRID 565422 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[CH2:6].[N+](=[CH:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N-]>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]2[CH2:6][CH:12]2[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:7]=[CH:8][CH:9]=1

Participants

3

Reactant 2

HCID 12192Ethyl diazoacetateHCID 676913-Fluorostyrene

Product 1

HCID 22111159HCID 22111159, compoundYield 55%

Procedure

3-Fluorostyrene (9.7 mL, 82 mmol) and ethyl diazoacetate (8.6 mL, 82 mmol) were reacted by the method reported in Org. Syn. Coll. Vol. VI, 1988, 913. The product was purified on silica. 9.4 g of ethyl 2-(3-fluorophenyl)cyclopropane carboxylate (45 mmol, 55%) was obtained. MS (GC/MS, EI) 208 (M+). (b) The trans ester was selectively hydrolyzed from the cis/trans mixture by the method reported in Org. Syn. Coll. Vol. VI, 1988, 913. Recrystallize from hexane to yield 2.5 g (13.9 mmol, 89% of the trans) of trans-2-(3-fluorophenyl)cyclopropane carboxylic acid. (c) The trans-2-(3-fluorophenyl)cyclopropane carboxylic acid (400 mg, 2.2 mmol) and (R)-3-methoxyphenyl ethylamine (280 mg, 1.9 mmol) were converted to the diastereomeric amides by the method reported in Aust. J. Chem. 1984, 37, 1709. 446 mg (1.4 mmol, 75%) of trans-2-(3-fluorophenyl)-N-(1(R))-(3-methoxyphenyl)ethyl)cyclopropane carboxamide was obtained. MS (GC/MS, EI) 313 (M+). (d) The mixture of diastereomeric amides (550 mg, 1.8 mmol) were reduced to the amines with BH3.THF (7 mL, 7.0 mmol) in 10 mL THF. Upon complete addition, the solution was heated to reflux, overnight. The solution was cooled to 0° C. and 7 mL of 6 N HCl was carefully added. This was stirred open to air for two hours, THF was removed in vacuo. The aqueous residue was basified to pH 9 with Na2CO3 solution and extracted with 3×20 mL CH2Cl2. The combined extracts were washed with 20 mL water and 20 mL of 1:1 water/brine. The organics were dried (Na2SO4), filtered, and solvent was removed. 520 mg of N-(trans-2-(3-fluorophenyl)cyclopropanylmethyl)-1-(R)-(3-methoxyphenyl)ethylamine (1.8 mmol, 99%) was obtained as an oil. MS (CI) m/z 300 (MH+).

Workup

  1. customThe product was purified on silica

Sources & evidence

ORD record
ord-1457227ea3574bf2a25dda6504f70d2d
Source dataset
uspto-grants-2001_01
Patent number
US06172091B2

Reaction notes

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