2-Fluoroethyl bromide → HCID 89662821, compound

HRID 1479100Notes

Reaction equation

HRID 1479100 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH2:25][NH:26][CH3:27])=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:28].Br[CH2:30][CH2:31][F:32].C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH2:25][N:26]([CH2:30][CH2:31][F:32])[CH3:27])=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:28]

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromide2×HCID 516892Sodium BicarbonateHCID 122436378HCID 122436378, compound

Product 1

HCID 89662821HCID 89662821, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Example 144 (100 mg; 0.23 mmol; 1 eq.), 1-bromo-2-fluoro-ethane (47 mg; 0.37 mmol; 1.6 eq.) and NaHCO3 (193 mg; 2.29 mmol; 10 eq.) in DMF was stirred at 100° C. for 30 minutes. 1-Bromo-2-fluoro-ethane (47 mg; 0.37 mmol; 1.6 eq.) was added and the resulting mixture was stirred at 100° C. for 30 minutes then concentrated in vacuo. After dilution with EA, the solution was washed with sat. aq. NaHCO3 then brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (EA to 10% MeOH in EA) afforded the title compound (50 mg, 49%) as a white foam. 1H NMR (DMSO-d6) δ 7.51-7.39 (m, 1H), 7.36-7.24 (m, 1H), 7.15 (d, J=8.3 Hz, 1H), 7.04 (t, J=7.3 Hz, 1H), 4.80 (d, J=7.3 Hz, 2H), 4.59 (d, J=19.7 Hz, 2H), 4.37 (td, J=5.0, 3.2 Hz, 1H), 4.21 (td, J=5.1, 3.3 Hz, 1H), 4.12 (t, J=5.3 Hz, 2H), 2.84 (s, 2H), 2.81 (s, 1H), 2.71 (t, J=5.2 Hz, 2H), 2.67-2.60 (m, 2H), 2.60-2.53 (m, 2H), 2.15 (s, 3H). HPLC (max plot) 97.5%, Rt 2.65 min. UPLC/MS: (MS+) 446.2 ([M+H]+).

Workup

  1. concentrationthen concentrated in vacuo
  2. washAfter dilution with EA, the solution was washed with sat. aq. NaHCO3
  3. dry with materialbrine, dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography (EA to 10% MeOH in EA)

Sources & evidence

ORD record
ord-0427f33592e940dbb3785c8625f18e1b
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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