Tetrahydrofuran → HCID 178520932, compound

HRID 2402614Notes

Reaction equation

HRID 2402614 reaction equation
C1COCC1.[Cl:6][C:7]1[C:8]2[N:9]([C:13]([C@H:16]3[CH2:21][CH2:20][C@H:19]([C:22](OC)=[O:23])[CH2:18][CH2:17]3)=[N:14][CH:15]=2)[CH:10]=[CH:11][N:12]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C(OCC)(=O)C>[Cl:6][C:7]1[C:8]2[N:9]([C:13]([C@H:16]3[CH2:17][CH2:18][C@H:19]([CH2:22][OH:23])[CH2:20][CH2:21]3)=[N:14][CH:15]=2)[CH:10]=[CH:11][N:12]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydride2×HCID 178501055HCID 178501055, compound

Product 1

HCID 178520932HCID 178520932, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A THF solution (1.00 L) of trans-methyl 4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexanecarboxylate (29.70 g, 101.1 mmol) was cooled to −78° C. and was charged with LAH (1M in THF, 25.3 mmol, 25.3 mL) dropwise. After 30 min., the reaction mixture was charged with additional LAH (25.3 mmol) at −78° C. and then, allowed to stir at −78° C. for 1.5 h. The reaction was slowly warmed up to rt and stirred for additional 30 min. Ethyl acetate, Na2SO4.10H2O, and silica gel were added to the reaction mixture and concentrated in vacuo to give an orange solid. The crude mixture was purified by a silica gel glass column chromatography (eluted with 2:3 EtOAc/DCM to 100% EtOAc) to obtain the title compound as a slightly yellow-tinted white solid; 1H NMR (CDCl3, 400 MHz) δ 1.14-1.30 (m, 2H), 1.61-1.75 (m, 1H), 1.84 (ddd, J=13.2, 13.2, 13.2, 3.2 Hz, 2H), 1.98-2.13 (m, 4H), 2.19 (s, br, —OH), 2.94 (tt, J=11.6, 3.2 Hz, 1H), 3.56 (d, J=6.0 Hz, 2H), 7.31 (d, J=5.2 Hz, 1H), 7.64 (dd, J=5.2, 1.2 Hz, 1H), 7.79 (d, J=0.8 Hz, 1H); MS (ES+): m/z 266.21/268.17 (100/89) [MH+]. HPLC: tR=2.38 min (OpenLynx, polar—5 min). MS (ES+): m/z 266.21 (100) [MH+], 268.17 (80) [MH+2], 289.18 (20) [MH+3]; tR(polar-5 min/openlynx) 2.36 min.

Workup

  1. temperatureThe reaction was slowly warmed up to rt
  2. stirringstirred for additional 30 min
  3. concentrationconcentrated in vacuo
  4. customto give an orange solid
  5. customThe crude mixture was purified by a silica gel glass column chromatography (eluted with 2:3 EtOAc/DCM to 100% EtOAc)

Sources & evidence

ORD record
ord-f5b1bef1869744e48964aa118f4130a1
Source dataset
uspto-grants-2014_08
Patent number
US08796455B2

Reaction notes

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