Ethyl diazoacetate → HCID 86693482, compound

HRID 575427Notes

Reaction equation

HRID 575427 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[CH:8]1[CH2:13][CH:6]([CH2:7]1)[C:5]2=[O:14].F[B-](F)(F)F.C([O+](CC)CC)C.[N+](=[CH:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[N-]>ClCCl>[Br:1][C:2]1[C:11]([F:12])=[CH:10][C:9]2[CH:8]3[CH2:7][CH:6]([CH2:13]3)[C:5](=[O:14])[CH:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 12192Ethyl diazoacetate2×HCID 2723982Triethyloxonium tetrafluoroborate2×HCID 86693064HCID 86693064, compound

Product 1

HCID 86693482HCID 86693482, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 6-bromo-7-fluoro-2,3-dihydro-1,3-methanonaphthalen-4(1H)-one (9.00 g, 35.3 mmol) in dry dichloromethane (180 mL) at 0° C. was introduced triethyloxonium tetrafluoroborate (141 mL of a 1.0M solution in dichloromethane, 141 mmol) dropwise over 15 minutes. A solution of ethyl diazoacetate (8.05 g in 75 mL dry dichloromethane, 70.6 mmol) was then added slowly over 20 minutes ensuring the reaction temperature did not rise >3° C. After 30 minutes, the reaction mixture was allowed to warm to room temperature for 16 hr. The solution was then re-cooled to 0° C. and re-treated with triethyloxonium tetrafluoroborate (141 mL of a 1.0M solution in dichloromethane, 141 mmol) and ethyl diazoacetate (8.05 g in 75 mL dry dichloromethane, 70.6 mmol) as described for the first treatment. After warming to room temperature for 5½ hours, the reaction mixture was washed with saturated aqueous sodium bicarbonate (3×100 mL washes), the organic phase dried over sodium sulfate and filtered under vacuum through a Celite 0 pad. The filtrate was adsorbed onto silica gel in vacuo and purified by silica gel flash column chromatography (heptanes/ethyl acetate gradient elution of increasing polarity) to furnish the title compound (8.70 g, 25.50 mmol, 72%) as a colorless solid: 1H NMR (500 MHz, CDCl3) δ 1.27 (t, J=7.09 Hz, 4H) 1.84 (dd, J=11.66, 6.62 Hz, 1H) 2.32 (dd, J=12.93, 6.94 Hz, 1H) 2.80 (dt, J=12.61, 7.88 Hz, 1H) 3.04 (dt, J=11.90, 8.55 Hz, 1H) 3.38 (ddd, J=8.83, 7.57, 3.78 Hz, 1H) 3.45 (td, J=8.20, 3.78 Hz, 1H) 4.18-4.29 (m, 2H) 4.78 (s, 1H) 6.88 (d, J=9.14 Hz, 1H) 7.48 (d, J=6.94 Hz, 1H); M+23=363/365.

Workup

  1. customdid not rise >3° C
  2. temperatureThe solution was then re-cooled to 0° C.
  3. temperatureAfter warming to room temperature for 5½ hours
  4. washthe reaction mixture was washed with saturated aqueous sodium bicarbonate (3×100 mL washes)
  5. dry with materialthe organic phase dried over sodium sulfate
  6. filtrationfiltered under vacuum through a Celite 0 pad
  7. custompurified by silica gel flash column chromatography (heptanes/ethyl acetate gradient elution of increasing polarity)

Sources & evidence

ORD record
ord-0fcb55b645bc456da7a467e98d2df91d
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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