Diethyl Ether → HCID 178459237, compound

HRID 1640658Notes

Reaction equation

HRID 1640658 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([C@H:11]3[CH2:16][CH2:15][C@H:14](C(OC)=O)[CH2:13][CH2:12]3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.[CH3:21][Mg]Br.CC[O:26][CH2:27][CH3:28]>C1(C)C=CC=CC=1.C1COCC1>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([C@H:11]3[CH2:16][CH2:15][C@H:14]([C:27]([OH:26])([CH3:28])[CH3:21])[CH2:13][CH2:12]3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 3283Diethyl Ether2×HCID 178418573HCID 178418573, compound2×HCID 178501055HCID 178501055, compound

Product 1

HCID 178459237HCID 178459237, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl trans-4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexanecarboxylate (4.0 g, 0.014 mol) in toluene (300 mL) and THF (70 mL) was cooled to 0° C. and treated with a 3.0 M solution of methylmagnesium bromide in ether (14 mL) maintaining the temperature at 0° C. The mixture was stirred at rt for 1.5 hours then cooled to 0° C. and an additional 3 eq of 3.0 M of methylmagnesium bromide in ether was added. The mixture was stirred at rt for 15 minutes then cooled 0° C. and quenched with 1:1 NH4Cl sat.: H2O (50 mL total volume). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo and the crude product thus obtained, chromatographed over silica gel eluting with EtOAc to afford desired 2-[trans-4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexyl]propan-2-ol. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.14-1.39 (m, 8 H), 1.41-1.60 (m, 1 H), 1.77-1.98 (m, 2 H), 2.01-2.20 (m, 4 H), 2.78-3.06 (m, 1 H), 7.35 (d, J=5.05 Hz, 1 H), 7.64 (d, J=5.05 Hz, 1 H) and 7.83 (s, 1 H).

Workup

  1. temperaturethen cooled to 0° C.
  2. stirringThe mixture was stirred at rt for 15 minutes
  3. temperaturethen cooled 0° C.
  4. customquenched with 1:1 NH4Cl sat.
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customthe crude product thus obtained
  10. customchromatographed over silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-a1762f4fed9541d8839f8d4fd351f1f2
Source dataset
uspto-grants-2012_02
Patent number
US08114846B2

Reaction notes

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