Hydrochloric Acid → HCID 66592688, compound

HRID 1092758Notes

Reaction equation

HRID 1092758 reaction equation
[F: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.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[ClH:29].CCCC[CH2:34][CH3:35]>C1COCC1>[F: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:25]2([OH:28])[CH2:24][CH2:23][N:22]([CH2:15]/[CH:16]=[CH:21]/[C:20]3[CH:19]=[CH:18][C:17]([Cl:29])=[CH:35][CH:34]=3)[CH2:27][CH2:26]2)[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8058HexaneHCID 192201-Benzyl-4-piperidoneHCID 310095N-(4-fluorophenyl)-2,2-dimethylpropanamide

Product 1

HCID 66592688HCID 66592688, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of n-buthyllithium in hexane (80.0 ml of a 1.6 M solution) was added dropwise to a solution of N-(4-fluoro-phenyl)-2,2-dimethyl-propionamide (10.0 g) in dry THF (200 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-benzyl-piperidin-4-one (9.20 ml) in THF (20 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 the 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 (8.3 g). M.p. 172-173° C.; Retention Time HPLC 1.47 min; MS (ES+) 385 (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-8760b027e9e84c77914b3ae7cc9e9bd9
Source dataset
uspto-grants-2012_03
Patent number
US08129534B2

Reaction notes

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