Sulfuric acid magnesium salt (1:1) → HCID 22278698, compound

HRID 1063265Notes

Reaction equation

HRID 1063265 reaction equation
[CH2:1]([C:3]1[C:4]([NH:23][CH:24]([CH3:31])[CH2:25][C:26](OCC)=[O:27])=[N:5][C:6]([CH2:21][CH3:22])=[C:7]([C:9]2[C:18]([O:19][CH3:20])=[CH:17][C:16]3[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)[N:8]=1)[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].[O-]S([O-])(=O)=O.[Mg+2]>C1COCC1>[CH2:1]([C:3]1[C:4]([NH:23][CH:24]([CH3:31])[CH2:25][CH2:26][OH:27])=[N:5][C:6]([CH2:21][CH3:22])=[C:7]([C:9]2[C:18]([O:19][CH3:20])=[CH:17][C:16]3[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)[N:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 22278778HCID 22278778, compound

Product 1

HCID 22278698HCID 22278698, compoundYield 85.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 250 mL dry round bottom flask equipped with a magnetic stir bar was charged with a solution of ethyl 3-{[3,6-diethyl-5-(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)pyrazin-2-yl]amino}butanoate (Example 38, 2.82 g, 6.62 mmol), in THF (37.6 mL) and cooled with an ice bath. A solution of 1M LAH in THF (33.11 mL, 33.11 mmol) was added to the reaction mixture dropwise. Strong effervescence was observed. The reaction was stirred at ° C. for an additional 15 minutes after the addition was complete, then the ice bath was removed and the reaction stirred at ambient temperature for 2 hours. The reaction color changed from pale yellow to brown. The reaction was cooled with an ice bath again, and quenched with ethyl acetate (33 mL) followed by the dropwsie addition of a saturated aqueous solution of KHSO4 (6.62 mL). Effervescence was observed again. After stirring at ° C. for 20 minutes the ice bath was removed. The addition of KHSO4 caused a gel to form, which turned into a solid within 30 minutes. MgSO4 was added to the mixture, and the heterogeneous solution was filtered through MgSO4. After rinsing with ethyl acetate, the filtrated was concentrated to give 2.74 grams of an auburn oil. This material was purified by Biotage MPLC (120 g column, 5% acetone in toluene) to give 2.16 grams (85%) of 3-{[3,6-diethyl-5-(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)pyrazin-2-yl]amino}butan-1-ol as a white foam. Rf 0.20 (40% ethyl acetate in heptane). IR (diffuse reflectance) 2965, 2931, 2875, 2859, 2835, 1572, 1493, 1463, 1445, 1391, 1309, 1248, 1232, 1205, 1171 cm−1. OAMS supporting ions at: ESI+ 384.2. HRMS (ESI) calcd for C23H33N3O2+H1 384.2651. found 384.2667. HRMS (ESI) calcd for C23H33N3O2+H1 384.2651. found 384.2667.

Workup

  1. customA 250 mL dry round bottom flask
  2. customequipped with a magnetic stir bar
  3. temperaturecooled with an ice bath
  4. additionfor an additional 15 minutes after the addition
  5. customthe ice bath was removed
  6. stirringthe reaction stirred at ambient temperature for 2 hours
  7. temperatureThe reaction was cooled with an ice bath again
  8. customquenched with ethyl acetate (33 mL)
  9. additionfollowed by the dropwsie addition of a saturated aqueous solution of KHSO4 (6.62 mL)
  10. stirringAfter stirring at ° C
  11. customfor 20 minutes the ice bath was removed
  12. additionThe addition of KHSO4
  13. customto form
  14. filtrationthe heterogeneous solution was filtered through MgSO4
  15. washAfter rinsing with ethyl acetate
  16. concentrationthe filtrated was concentrated
  17. customto give 2.74 grams of an auburn oil
  18. customThis material was purified by Biotage MPLC (120 g column, 5% acetone in toluene)

Sources & evidence

ORD record
ord-54f5d8c513b24e74908fe925e56fb973
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

Loading…