Hydrochloric Acid → HCID 14722778, compound

HRID 1987062Notes

Reaction equation

HRID 1987062 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2.[Cl:17][CH2:18][C:19](N(OC)C)=[O:20].Cl.C([O-])(O)=O.[Na+]>CCOCC.C1COCC1>[Cl:17][CH2:18][C:19]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)=[O:20]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1401098-BromoquinolineHCID 516892Sodium BicarbonateHCID 27347162-Chloro-N-methoxy-N-methylacetamideHCID 178418339Butyllithium

Product 1

HCID 14722778HCID 14722778, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of n-BuLi (28 mL, 44.0 mmol, 1.6M in hexanes) at −78° C. was added a solution of 8-bromoquinoline (8.5 g, 40.0 mmol) in Et2O (60 mL) over 20 minutes. After stirring for 22 minutes, a solution of 2-chloro-N-methoxy-N-methylacetamide (5.7 g, 41 mmol) in THF (35 mL) was added over 12 minutes (see Tillyer, R. et al; Synlett 225-226, 1996; and Dolling, U. H. et al; U.S. Pat. No. 5,786,515). After 3 hours the reaction was poured into 11 mL, 4N HCl. The aqueous phase was neutralized to pH 7 using solid NaHCO3 and partitioned with Et2O (2×100 mL). The combined organic phase was washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo. Purification via SiO2 chromatography (20% EtOAc/hexanes) afforded the product as a yellow solid (4.2 g). 1H NMR (300 Hz, CDCl3) δ 9.0-8.96 (m, 1H), 8.26-8.19 (m, 2H), 8.04-8.01 (m, 1H), 7.68-7.63 (m, 1H), 7.52-7.48 (m, 1H), 5.37 (s, 2H).

Workup

  1. custompartitioned with Et2O (2×100 mL)
  2. washThe combined organic phase was washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification via SiO2 chromatography (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-385f72395d7245c9b341a94fde528583
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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