Isobutylene → 3-Cyclohexyl-1-[4-[4-[2-(1,1-dimethylethoxy)phenyl]-1-piperidinyl]butan-1-yl]-2-imidazolidinone Oxalate

HRID 1057669Notes

Reaction equation

HRID 1057669 reaction equation
[CH:1]1([N:7]2[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][CH:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[OH:28])[CH2:18][CH2:17]3)[C:8]2=[O:29])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:30]([O:34][C:35](N1CCC(C2C=CC=CC=2O)CC1)=[O:36])([CH3:33])([CH3:32])[CH3:31].ClCCCCN1CCN(C2CCCCC2)[C:56]1=[O:66].CC(=C)C.FC(F)(F)S(O)(=O)=O>C(Cl)Cl.C(N(CC)CC)C>[C:56]([OH:66])(=[O:28])[C:35]([OH:36])=[O:34].[CH:1]1([N:7]2[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][CH:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:18][CH2:17]3)[C:8]2=[O:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 8255IsobutyleneHCID 62406Trifluoromethanesulfonic acidHCID 17174861Tert-butyl 4-(2-hydroxyphenyl)piperidine-1-carboxylateHCID 186721001-(4-Chloro-1-butyl)-3-cyclohexyl-2-imidazolidinoneHCID 186721333-Cyclohexyl-1-[4-[4-(2-hydroxyphenyl)-1-piperidinyl]butan-1-yl]-2-imidazolidinone

Product 1

HCID 186721233-Cyclohexyl-1-[4-[4-[2-(1,1-dimethylethoxy)phenyl]-1-piperidinyl]butan-1-yl]-2-imidazolidinone Oxalate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 3-cyclohexyl-1-[4-[4-(2-hydroxyphenyl)-1-piperidinyl]butan-1-yl]-2-imidazolidinone (1 g, prepared from 4-(2-hydroxyphenyl)piperidine (described in Example 5) and 1a by the method described in Example 4) in dry methylene chloride (10 ml) was cooled to −20° C. Isobutylene (5 ml, condensed at −25° C.) was added under a nitrogen atmosphere followed by addition of trifluoromethanesulfonic acid (0.4 ml). The mixture was stirred for 3 h at −20° C. followed by addition of triethylamine (2 mL). After warming to room temperature the reaction mixture was concentrated in vacuo followed by addition of 2 M ammonia and extraction with methylene chloride. The organic phase was dried over magnesium sulfate and concentrated in vacuo leaving an oil which was purified by flash chromatography (silica gel, eluent: ethyl acetate/MeOH/triethylamine 97:2:1). The resulting colorless oil was dissolved in a mixture of ethyl acetate and acetone. Addition of oxalic acid gave the title compound, 10a, as a crystalline material. Yield: 0.8 g, mp: 147-53° C. 1H NMR (DMSO-d6): δ 0.95-2.10 (m, 18H), 1.35 (s, 9H), 2.85-3.15 (m, 7H), 3.25 (s, 4H), 3.35-3.60 (m, 3H), 6.90-7.25 (m, 4H).

Workup

  1. temperatureAfter warming to room temperature the reaction mixture
  2. concentrationwas concentrated in vacuo
  3. additionfollowed by addition of 2 M ammonia and extraction with methylene chloride
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customleaving an oil which
  7. customwas purified by flash chromatography (silica gel, eluent: ethyl acetate/MeOH/triethylamine 97:2:1)
  8. dissolutionThe resulting colorless oil was dissolved in a mixture of ethyl acetate and acetone
  9. additionAddition of oxalic acid

Sources & evidence

ORD record
ord-b9faefed9e224b9a853644e6c19d17d8
Source dataset
uspto-grants-2003_02
Patent number
US06514993B1

Reaction notes

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