N,N,N',N'-Tetramethylethylenediamine → HCID 57935988, compound

HRID 1434602Notes

Reaction equation

HRID 1434602 reaction equation
CN(CCN(C)C)C.[F:9][C:10]1[CH:11]=[C:12]([Mg]Br)[CH:13]=[C:14]([F:16])[CH:15]=1.CN1[C@@H](C)[C@@H](C2C=CC=CC=2)N([C:32](=[O:41])/[CH:33]=[CH:34]/[CH:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)C1=O.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.[Cl-].[NH4+]>C1COCC1.ClCCl.[Cu](I)I.C(OCC)(=O)C>[F:9][C:10]1[CH:11]=[C:12]([C@@H:34]([CH:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH2:33][CH:32]=[O:41])[CH:13]=[C:14]([F:16])[CH:15]=1

Participants

10

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 57936006HCID 57936006, compoundHCID 178418657HCID 178418657, compoundHCID 178505930HCID 178505930, compound

Product 1

HCID 57935988HCID 57935988, compound

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

To a suspension of copper iodide (931 mg) in anhydrous THF (60 ml) under argon was added TMEDA (0.81 ml) and the resulting mixture was stirred for 20 minutes. The reaction mixture was cooled to −70° C. and 3,5-difluorophenyl magnesium bromide (9.8 ml of 0.5M solution in THF) was added dropwise and the mixture was stirred for a further 1 hour. A preformed solution of (4R,5S)-1,5-dimethyl-4-phenyl-3-[(2E)-3-(tetrahydro-2H-pyran-4-yl)prop-2-enoyl]imidazolin-2-one (800 mg) and dibutylboron triflate (2.93 ml of 1M solution in dichloromethane) in dichloromethane (2 ml) was added dropwise to the mixture. The reaction mixture was stirred for 1 hour at −70° C. and allowed to warm to room temperature, then saturated ammonium chloride (100 ml) and ethyl acetate (200 ml) was added. Air was blown through the mixture for 1 hour. The ethyl acetate was collected and the aqueous layer was extracted with ethyl acetate (2×100 ml). The combined ethyl acetate layers were washed with water, saturated EDTA, dried and evaporated to dryness. The residue was purified by chromatography on silica eluting with a solvent gradient of isohexane to 75% ethyl acetate/isohexane to give the title compound as a solid. Yield 887 mg. M+H 443. NMR CDCl3 0.8 (d, 3H), 1.2-1.5 (m, 3H), 1.7 (m, 2H), 2.85 (s, 3H), 3.0 (m, 1H), 3.15-3.4 (m, 3H), 3.8-4.0 (m, 4H), 5.2 (d, 1H), 6.6-6.7 (m, 3H), 6.85 (m, 2H), 7.2 (m, 3H).

Workup

  1. stirringthe mixture was stirred for a further 1 hour
  2. stirringThe reaction mixture was stirred for 1 hour at −70° C.
  3. temperatureto warm to room temperature
  4. waitAir was blown through the mixture for 1 hour
  5. customThe ethyl acetate was collected
  6. extractionthe aqueous layer was extracted with ethyl acetate (2×100 ml)
  7. washThe combined ethyl acetate layers were washed with water, saturated EDTA
  8. customdried
  9. customevaporated to dryness
  10. customThe residue was purified by chromatography on silica eluting with a solvent gradient of isohexane to 75% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-1e25ae6b588c4aabbda8317a6ad2b92e
Source dataset
uspto-grants-2009_11
Patent number
US07615555B2

Reaction notes

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