Dimethylformamide → HCID 86693512, compound

HRID 575450Notes

Reaction equation

HRID 575450 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Br:6][C:7]1[C:8]([F:20])=[CH:9][C:10]2[CH:16]3[CH2:17][CH:14]([CH2:15]3)[C:13](=O)[CH2:12][C:11]=2[CH:19]=1.CN(C)[CH:23]=[O:24]>>[Br:6][C:7]1[C:8]([F:20])=[CH:9][C:10]2[CH:16]3[CH2:17][CH:14]([CH2:15]3)[C:13]([Cl:3])=[C:12]([CH:23]=[O:24])[C:11]=2[CH:19]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 866935132-bromo-3-fluoro-6,7-dihydro-5H-5,7-methanobenzo[7]annulen-8(9H)-one

Product 1

HCID 86693512HCID 86693512, compound

Procedure

To anhydrous N,N-dimethylformamide (0.1 mL) at 0-5° C. under an atmosphere of nitrogen was introduced phosphorous oxychloride (0.09 mL, 0.94 mmol) dropwise over 10 minutes and the reaction mixture warmed to room temperature for 1 hr. The reaction mixture was cooled to +5-10° C. and a solution of 2-bromo-3-fluoro-6,7-dihydro-5H-5,7-methanobenzo[7]annulen-8(9H)-one (100 mg, 0.37 mmol) in anhydrous N,N-dimethylformamide (0.2 mL) introduced. After 1 hr at this temperature, the reaction mixture was warmed to 72° C. for 3.5 hr. After cooling to room temperature, ice-water (−5 mL) was introduced and the aqueous solution extracted with ethyl acetate (2×5 mL). The combined ethyl acetate extracts were dried over sodium sulfate, filtered and evaporated in vacuo to furnish the crude title compound (125 mg at 79% purity LC-MS (UV215) as an orange wax. This compound was carried through to the next synthetic step without further purification: 1H NMR (500 MHz, CDCl3) δ1.66-1.74 (m, 2H), 2.76-2.84 (m, 2H), 3.36 (td, J=7.88, 4.10 Hz, 1H), 3.48 (td, J=7.88, 4.10 Hz, 1H), 6.91 (d, J=8.83 Hz, 1H), 7.96 (d, J=7.25 Hz, 1H), 10.33 (s, 1H)

Workup

  1. temperatureThe reaction mixture was cooled to +5-10° C.
  2. temperaturethe reaction mixture was warmed to 72° C. for 3.5 hr
  3. temperatureAfter cooling to room temperature
  4. extractionthe aqueous solution extracted with ethyl acetate (2×5 mL)
  5. dry with materialThe combined ethyl acetate extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-37a4a1da1c1f4b379ce6b4a8873f7bc1
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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