Hydrochloric Acid → HCID 59337708, compound

HRID 12395Notes

Reaction equation

HRID 12395 reaction equation
[OH-].[K+].FC(F)(F)C([N:7]1[CH2:22][CH2:21][C:10]2([C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12](=[O:20])[CH2:11]2)[CH2:9][CH2:8]1)=O.Cl.C(N(CC)CC)C.[C:33](Cl)(=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35]>O.CO>[C:33]([N:7]1[CH2:8][CH2:9][C:10]2([C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12](=[O:20])[CH2:11]2)[CH2:21][CH2:22]1)(=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 62493Pivaloyl chlorideHCID 19366988HCID 19366988, compound

Product 1

HCID 59337708HCID 59337708, compoundYield 79.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

KOH (0.65 g, 11.5 mmol) in water (3.0 mL) was added to 19b (1.20 g, 3.8 mmol) in methanol (15 mL) and stirred at rt overnight. The reaction was neutralized with conc. HCl (1 mL) and then concentrated. The crude reaction mixture was evaporated from toluene to remove water. The crude amine was taken up in dichloromethane (30 mL) and triethylamine (2.5 mL, 19.2 mmol) and pivaloyl chloride (0.9 mL, 7.7 mmol) were added. This was stirred at rt for 4 h and then water was added to quench the reaction. The aqueous layer was extracted with dichloromethane (3×) and the combined organics were dried (MgSO4), filtered and evaporated to give the crude product. The crude product was purified by flash chromatography on Biotage using EtOAc/Hexanes (50-100%) to give 19c as a white solid (0.91 g, 79%). (M+H)+=301. 1H NMR (400 MHz, CDCl3) δ ppm 7.90 (s, 1H); 7.30 (d, J=7.3 Hz, 1H); 7.22 (t, J=7.7 Hz, 1H); 7.08 (t, J=7.6 Hz, 1H); 6.78 (d, J=7.8 Hz, 1H); 4.30 (m, 2H); 3.18 (m, 2H); 2.75 (s, 2H); 1.91 (m, 2H); 1.71 (m, 2H); 1.28 (s, 9H).

Workup

  1. concentrationconcentrated
  2. customThe crude reaction mixture
  3. customwas evaporated from toluene
  4. customto remove water
  5. stirringThis was stirred at rt for 4 h
  6. customto quench
  7. customthe reaction
  8. extractionThe aqueous layer was extracted with dichloromethane (3×)
  9. dry with materialthe combined organics were dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customto give the crude product
  13. customThe crude product was purified by flash chromatography on Biotage

Sources & evidence

ORD record
ord-d600e7c22e20492bb1c7c43362c150ef
Source dataset
uspto-grants-2010_06
Patent number
US07728008B2

Reaction notes

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