2-Fluoroethyl bromide → HCID 89652850, compound

HRID 1479073Notes

Reaction equation

HRID 1479073 reaction equation
Br[CH2:2][CH2:3][F:4].[Cl:5][C:6]1[C:14]([CH3:15])=[N:13][C:12]2[N:8]([N:9]=[C:10]3[CH2:18][N:17]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=4[O:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[O:20])[CH2:16][C:11]3=2)[C:7]=1[CH3:35].C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:5][C:6]1[C:14]([CH3:15])=[N:13][C:12]2[N:8]([N:9]=[C:10]3[CH2:18][N:17]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=4[O:28][CH:29]4[CH2:34][CH2:33][N:32]([CH2:2][CH2:3][F:4])[CH2:31][CH2:30]4)=[O:20])[CH2:16][C:11]3=2)[C:7]=1[CH3:35]

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromide2×HCID 516892Sodium BicarbonateHCID 71610191HCID 71610191, compound

Product 1

HCID 89652850HCID 89652850, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1-Bromo-2-fluoro-ethane (19 mg; 0.15 mmol; 1.1 eq.) was added to a suspension of Example 64 (60 mg; 0.14 mmol; 1 eq.) and NaHCO3 (114 mg; 1.35 mmol; 10 eq.) in DMF (2 mL) and the reaction mixture was stirred at 100° C. (MW heating) for 30 minutes. 1-Bromo-2-fluoro-ethane (9 mg; 0.07 mmol; 0.5 eq.) was added and the reaction mixture was stirred at 100° C. (MW heating) for 30 minutes. The precipitate was filtered off and the mother liquor was concentrated in vacuo. The residue was diluted with DCM, washed with 1M NaOH, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (5% to 20% MeOH in DCM) followed by crystallization from EA afforded the title compound (33 mg, 49%) as yellow solid. 1H NMR (CDCl3) δ 7.40-7.28 (m, 1H), 6.84-6.61 (m, 2H), 5.11-4.90 (m, 2H), 4.66 (br s, 2H), 4.56 (t, J=4.9 Hz, 1H), 4.46-4.29 (m, 2H), 2.91 (s, 1.8H), 2.86 (s, 1.2H), 2.73-2.48 (m, 7H), 2.47-2.30 (m, 2H), 2.07-1.91 (m, 2H), 1.91-1.73 (m, 2H). HPLC (max plot) 98.5%, Rt 2.96 min. UPLC/MS: (MS+) 490.3 ([M+H]+).

Workup

  1. temperature(MW heating) for 30 minutes
  2. stirringthe reaction mixture was stirred at 100° C.
  3. temperature(MW heating) for 30 minutes
  4. filtrationThe precipitate was filtered off
  5. concentrationthe mother liquor was concentrated in vacuo
  6. additionThe residue was diluted with DCM
  7. washwashed with 1M NaOH
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (5% to 20% MeOH in DCM)
  11. customfollowed by crystallization from EA

Sources & evidence

ORD record
ord-8c696d5f74384debb0951fe8688785e5
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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