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Water → 3-[(R*)-1-((S)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-3-yl]-phenol

HRID 2366044
Notes
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Reaction equation

HRID 2366044 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]2[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=2)[CH2:2]1.C(=O)(O)[O-].[Na+].[CH2:19]([O:26][C:27]1[C:36]2[O:35][CH2:34][C@H:33]([CH2:37]OS(C)(=O)=O)[O:32][C:31]=2[CH:30]=[CH:29][CH:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>CN(C)C=O.C(OCC)(=O)C>[CH2:19]([O:26][C:27]1[C:36]2[O:35][CH2:34][C@H:33]([CH2:37][N:1]3[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]4[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=4)[CH2:2]3)[O:32][C:31]=2[CH:30]=[CH:29][CH:28]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 12937952Phenol, 3-(3R)-3-piperidinyl-HCID 86644728Methanesulfonic acid (R)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester

Product 1

HCID 684875373-[(R*)-1-((S)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-3-yl]-phenolYield 33.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of hydrochloride salt of (R*)-3-(piperidin-3-yl)-phenol (240 mg, 1.12 mmol) and sodium bicarbonate in N,N-dimethylformamide (3 ml) were stirred at +120° C. under nitrogen atmosphere. To this mixture, a mixture of methanesulfonic acid (R)-5-benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester (390 mg, 1.11 mmol) in N,N-dimethylformamide (3 ml) was added, and stirred at +130° C. for 3.5 h. The reaction mixture was cooled down, water (20 ml) and ethyl acetate (15 ml) were added and the layers were separated. Organic phase was recovered and water layer was extracted twice with ethyl acetate. Organic phase and ethyl acetate extracts were combined and washed five times with water and saturated sodium chloride solution. The combined organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified with flash chromatography using heptane and ethyl acetate as eluents to give 160 mg of the title compound.

Workup

  1. additionwas added
  2. stirringstirred at +130° C. for 3.5 h
  3. temperatureThe reaction mixture was cooled down
  4. customthe layers were separated
  5. customOrganic phase was recovered
  6. extractionwater layer was extracted twice with ethyl acetate
  7. washwashed five times with water and saturated sodium chloride solution
  8. dry with materialThe combined organic phase was dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customThe crude product was purified with flash chromatography

Sources & evidence

ORD record
ord-c6fb91e89fb841118edde152790b3ac3
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08697723B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes