Diiodomethane → HCID 66734076, compound

HRID 1929720Notes

Reaction equation

HRID 1929720 reaction equation
[CH2:1]([Zn]CC)C.CCCCCC.C(O)(C(F)(F)F)=O.C(I)I.C(OC([N:29]1[CH2:34][CH2:33][N:32]2[C:35]([CH3:40])=[N:36][C:37]([CH:38]=[CH2:39])=[C:31]2[CH:30]1[CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=1)=O)(C)(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:38]1([C:37]2[N:36]=[C:35]([CH3:40])[N:32]3[CH2:33][CH2:34][NH:29][CH:30]([CH2:41][CH2:42][C:43]4[CH:48]=[CH:47][C:46]([C:49]([F:50])([F:52])[F:51])=[CH:45][CH:44]=4)[C:31]=23)[CH2:39][CH2:1]1

Participants

8

Reactant 6

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 8058HexaneHCID 516892Sodium BicarbonateHCID 66733853HCID 66733853, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 66734076HCID 66734076, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 1M diethylzinc in hexane (37.0 ml; 37.000 mmol) in anhydrous DCM (40 ml) was added dropwise a solution of TFA (2.82 ml; 36.924 mmol) in anhydrous DCM (20 ml). After 30 min., a solution of methylene iodide (2.97 ml; 36.924 mmol) in anhydrous DCM (20 ml) was added dropwise to the reaction mixture, and stirring at 0° C. was continued for 10 min. A solution of 3-methyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-1-vinyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (0.536 g; 1.231 mmol) in anhydrous DCM (5 ml) was then added dropwise, and the resulting mixture was further stirred at 0° C. for 1 h, and finally at rt for 6 h. The reaction mixture was then treated dropwise with TEA (7 ml), and with an aq. sat. solution of NaHCO3 (50 ml). The organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH/25% aq. NH4OH, 200/10/1) afforded the target compound 1-cyclopropyl-3-methyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine as a yellow solid (0.186 g; 34%). LC-MS: tR=0.68 min.; [M+H]+=350.42 g/mol.

Workup

  1. waitwas continued for 10 min
  2. stirringthe resulting mixture was further stirred at 0° C. for 1 h
  3. waitfinally at rt for 6 h
  4. dry with materialThe organic layer was dried over anh. MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customPurification by FC (DCM/MeOH/25% aq. NH4OH, 200/10/1)

Sources & evidence

ORD record
ord-a8fcf1edcdce41059983dacebe8635db
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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