Hydrochloric Acid → HCID 57577277, compound

HRID 2167186Notes

Reaction equation

HRID 2167186 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19](/[CH:22]=[CH:23]/[CH2:24][N:25]2[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]2)=[CH:18][CH:17]=1.Cl>CCCCCC.C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[C:6]([C:28]2([OH:31])[CH2:27][CH2:26][N:25]([CH2:24]/[CH:23]=[CH:22]/[C:19]3[CH:18]=[CH:17][C:16]([Cl:15])=[CH:21][CH:20]=3)[CH2:30][CH2:29]2)[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 182511Propanamide, N-(4-chlorophenyl)-2,2-dimethyl-HCID 58046560HCID 58046560, compound

Product 1

HCID 57577277HCID 57577277, compoundYield 44.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of n-buthyllithium in hexane (47.0 ml of a 1.6 M solution) was added dropwise to a solution of N-(4-chloro-phenyl)-2,2-dimethyl-propionamide (6.35 g) in dry THF (100 ml) at −5° C. under a N2 atmosphere over 15 min. The resulting solution was stirred at 0° C. for 2 hours, and then a solution of 1-[(E)-3-(4-chloro-phenyl)-allyl]-piperidin-4-one (7.49 g) in THF (15 ml) was added dropwise to the above solution of the dianion at 0° C. over a 1 hour period. The reaction mixture was stirred for 2 hours at 0° C. and then overnight at r.t. The solution was then poured into ice water, made acidic with conc. HCl and extracted with ethyl acetate. The water layer was made basic and extracted three times with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was subjected to silica gel chromatography (hexane:ethyl acetate:triethyl amine 49:49:2) to afford the title product (6.2 g). M.p. 177-179° C.; Retention Time HPLC 2.19 min; MS (ES+) 461 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred for 2 hours at 0° C.
  2. customovernight
  3. customat r.t
  4. extractionextracted with ethyl acetate
  5. extractionextracted three times with ethyl acetate
  6. washThe combined organic layers were washed with water
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f48c88f54c044f8a8fce8ce1c38303d0
Source dataset
uspto-grants-2015_06
Patent number
US09045422B2

Reaction notes

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