Dimethylformamide → HCID 10276457, compound

HRID 1991146Notes

Reaction equation

HRID 1991146 reaction equation
C([O:5][C:6](=[O:25])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([CH3:23])[CH:17]=2)=[CH:11][C:10]=1[CH3:24])(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.[F:37][C:38]([F:48])([F:47])[C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1>O>[CH3:24][C:10]1[CH:11]=[C:12]([S:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:43][C:42]3[CH:41]=[CH:40][C:39]([C:38]([F:37])([F:47])[F:48])=[CH:46][CH:45]=3)=[C:18]([CH3:23])[CH:17]=2)[CH:13]=[CH:14][C:9]=1[O:8][CH2:7][C:6]([OH:5])=[O:25]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 20768134HCID 20768134, compound

Product 1

HCID 10276457HCID 10276457, compoundYield 41.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

An oven-dried 100 mL round-bottomed flask was charged with compound 1.1 (400 mg, 1.1 mmol), finely powdered Cs2CO3 (405 mg, 1.2 mmol), and anhydrous DMF (2 mL). 4-(Trifluoromethyl)benzyl bromide (298 mg, 1.1 mmol, Aldrich) was added, and the reaction was stirred vigorously overnight at room temperature. The reaction mixture was poured into 60 mL of water and extracted with 3×20 mL of methylene chloride. The combined organics were washed with 2×50 mL of water, dried over Na2SO4, and concentrated to a slightly yellow oil (422 mg). This crude material was dissolved in methylene chloride (2.5 mL), and trifluoroacetic acid (1.2 mL) was slowly added. The reaction was stirred for 4 h, after which the volatile components were removed in vacuo to reveal a crude pink oil. The crude pink oil was purified using flash chromatography (SiO2 gel 60, eluted with 60% EtOAc/hexanes), and the resulting white solid was recrystallized from methylene chloride/hexanes to give fine white crystals (213 mg). MS ESI m/e: 461.1 (M−H). 1H NMR (400 MHz) (CDCl3) δ 7.65 (2H, d, J=8.4 Hz); 7.54 (2H, d, J=8.4 Hz); 7.20 (1H, s); 7.17-7.14 (2H, d, m); 7.10 (1H, dd, J=13.0, 2.4 Hz); 6.77 (1H, d, J=8.4 Hz); 6.65 (1H, d, J=8.4 Hz); 5.12 (2H, s); 4.66 (2H, s); 2.25 (3H, s); 2.24 (3H, s).

Workup

  1. extractionextracted with 3×20 mL of methylene chloride
  2. washThe combined organics were washed with 2×50 mL of water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a slightly yellow oil (422 mg)
  5. dissolutionThis crude material was dissolved in methylene chloride (2.5 mL)
  6. additiontrifluoroacetic acid (1.2 mL) was slowly added
  7. stirringThe reaction was stirred for 4 h
  8. customafter which the volatile components were removed in vacuo
  9. customThe crude pink oil was purified
  10. washflash chromatography (SiO2 gel 60, eluted with 60% EtOAc/hexanes)
  11. customthe resulting white solid was recrystallized from methylene chloride/hexanes

Sources & evidence

ORD record
ord-4c8c4561efd34bd6be80e8886e0837ea
Source dataset
uspto-grants-2010_01
Patent number
US07645779B2

Reaction notes

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