Benzyl Bromide → HCID 53401373, compound

HRID 1005056Notes

Reaction equation

HRID 1005056 reaction equation
CCCCCC.[OH:7][CH:8]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[CH2:12][CH2:11][N:10]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:9]1.C(=O)([O-])[O-].[K+].[K+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C)C=O.C(OCC)(=O)C>[CH2:34]([O:20][C:17]1[CH:16]=[CH:15][C:14]([CH:13]2[CH2:12][CH2:11][N:10]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:9][CH:8]2[OH:7])=[CH:19][CH:18]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 7498Benzyl Bromide2×HCID 8058HexaneHCID 11430Potassium Carbonate2×HCID 21713087(3S,4S)-tert-Butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 53401373HCID 53401373, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In an analogous manner to that described in Example 22(k), by acylating (3RS,4RS)-4-[4-(3-hydroxy-propoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate with benzoyl chloride there was obtained tert-butyl (3RS,4RS)-4-[4-(3-benzoyloxy-propoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless oil; Rf : 0.84 (SiO2, hexane:ethyl acetate=1:1). (d) A mixture of 1.0 g (3.41 mmol) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate, 471 mg (34.1 mmol, 10 eq.) of potassium carbonate and 607 ml (5.11 mmol, 1.5 eq.) of benzyl bromide in 30 ml of dimethylformamide was stirred at room temperature for 2 hours and at 80° C. for 15 hours. Subsequently, 471 mg (34.1 mmol, 10 eq.) of potassium carbonate and 607 ml (5.11 mmol, 1.5 eq.) of benzyl bromide were again added and the mixture was stirred at 80° C. for a further 6 hours. The reaction mixture, cooled to room temperature, was poured into 300 ml of an ice/water mixture and extracted three times with 250 ml of ethyl acetate. The organic phases were washed once with water and once with saturated sodium chloride solution, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The yellow oil (1.82 g) was separated on silica gel using an eluent gradient of 4:1 to 3:2 of a mixture of hexane and ethyl acetate as the eluent. There were obtained 620 mg (72% of theory) of tert-butyl (3RS,4RS)-4-(4-benzyloxy-phenyl)-3-hydroxy-piperidine-1-carboxylate which, after recrystallization from a mixture of methylene chloride and hexane, gave 361 mg (28% of theory) as a white, crystalline product; MS: 383 (M)+.

Workup

  1. stirringthe mixture was stirred at 80° C. for a further 6 hours
  2. temperatureThe reaction mixture, cooled to room temperature
  3. extractionextracted three times with 250 ml of ethyl acetate
  4. washThe organic phases were washed once with water and once with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customevaporated under reduced pressure
  7. customdried in a high vacuum
  8. customThe yellow oil (1.82 g) was separated on silica gel using an eluent gradient of 4:1
  9. additionto 3:2 of a mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-b632044887fb4a278aa158226eeeabb6
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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