1,2-Dimethoxyethane → HCID 67543225, compound

HRID 1809797Notes

Reaction equation

HRID 1809797 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](Br)[CH:15]=2)[C@@H:10]([O:21][CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(COC)OC.C([O-])([O-])=O.[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:15]=[C:16]([C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([OH:33])[CH:39]=3)[CH:17]=[CH:18][CH:19]=2)[C@@H:10]([O:21][CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 67542570HCID 67542570, compound

Product 1

HCID 67543225HCID 67543225, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

A stirred mixture of (3R*,4R*)-4-(3-bromo-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid t-butyl ester (150 mg, 0.3 mmol), 3-hydroxyphenylboronic acid (48 mg, 0.35 mmol), dimethoxyethane (3 mL), H2O (1 mL), tetrakis-(triphenylphosphin)-palladium (21 mg, 0.02 mmol) and Na2CO3 (47 mg, 0.45 mmol) is heated at reflux under argon for 16 h. The mixture is cooled to RT, dimethoxyethane is removed in vacuo and the residue is diluted with aqueous 2N Na2CO3 solution containing a few mL of concentrated NH4OH. The aqueous layer is extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4) and evaporated in vacuo. Flash chromatography of the dark residue (SiO2, hexane/ethyl acetate) affords (3R*,4R*)-4-(3′-hydroxy-biphenyl-3-yl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid t-butyl ester as a yellowish resin: MS 508.4 [M−H]−; retention time 8.01 min (HPLC, Nucleosil C18; 5-100% CH3CN in H2O within 8 min, then 100% CH3CN for 2 min).

Workup

  1. temperatureis heated
  2. temperatureat reflux under argon for 16 h
  3. customdimethoxyethane is removed in vacuo
  4. additionthe residue is diluted with aqueous 2N Na2CO3 solution
  5. additioncontaining a few mL of concentrated NH4OH
  6. extractionThe aqueous layer is extracted three times with CH2Cl2
  7. dry with materialThe combined organic extracts are dried (Na2SO4)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-6665841ae7ee42b1854553ea635d9416
Source dataset
uspto-grants-2013_01
Patent number
US08362040B2

Reaction notes

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