Acetic Acid → HCID 49867582, compound

HRID 1005250Notes

Reaction equation

HRID 1005250 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][N:11](C([C@@]34C(C)(C)[C@@](C)(CC3)C(=O)O4)=O)[CH2:10][C@@H:9]2[O:27][CH2:28][C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)=[CH:4][CH:3]=1.CNC(NCCC[C@H](N)C(O)=O)=NC.C(O)(=O)C>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][NH:11][CH2:10][C@@H:9]2[O:27][CH2:28][C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 16914830344-00-4HCID 57295318HCID 57295318, compound

Product 1

HCID 49867582HCID 49867582, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

A solution of 736 mg (1.28 mmol) of (3R,4R)-4-(4-bromophenyl)-3-(naphthalen-2-ylmethoxy)-1-[(1 S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl]-piperidine in 32 ml of absolute tetrahydrofuran was cooled to -70° C. Thereto there was added dropwise a solution of 1.86 ml (6.5 mmol) of sodium dihydrido-bis-(2-methoxyethoxy)-aluminate (70% in toluene, about 3.5M) in 32 ml of tetrahydrofuran. The mixture was warmed to -40° C., stirred at -40° C. for 8 hours, thereafter cooled to -78° C. and treated dropwise with a solution of 0.5 ml of glacial acetic acid in 10 ml of tetrahydrofuran. For the working-up, the reaction mixture was partitioned between 200 mg of ethyl acetate and 200 ml of aqueous 5% sodium hydrogen carbonate solution. The organic phase was separated and the aqueous phase was back-extracted three times with 50 ml of ethyl acetate each time. The combined organic phases were dried over magnesium sulphate and finally the solvent was distilled off under reduced pressure. The crude product (800 mg) was purified by chromatography on silica gel with a 9:1 mixture of methylene chloride and methanol as the eluent. There were obtained 344 mg (68% of theory) of (3R,4R)-4-(4-bromophenyl)-3-(naphthalen-2-ylmethoxy)-piperidine as a colourless solid; MS: 396, 398 (M+H)+.

Workup

  1. temperaturecooled to -78° C.
  2. customthe reaction mixture was partitioned between 200 mg of ethyl acetate and 200 ml of aqueous 5% sodium hydrogen carbonate solution
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was back-extracted three times with 50 ml of ethyl acetate each time
  5. dry with materialThe combined organic phases were dried over magnesium sulphate
  6. distillationfinally the solvent was distilled off under reduced pressure
  7. customThe crude product (800 mg) was purified by chromatography on silica gel with a 9:1 mixture of methylene chloride and methanol as the eluent

Sources & evidence

ORD record
ord-b13f2a2a61c54f25a5375b42ec88451f
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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