Triphenylphosphine → methyl 4-(tert-butyl)-2-(1-Boc-piperidin-4-yloxy)benzoate

HRID 1445455Notes

Reaction equation

HRID 1445455 reaction equation
[C:1]([C:5]1[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([OH:15])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:16]([N:23]1[CH2:28][CH2:27][CH:26](O)[CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[C:19]([O:18][C:16]([N:23]1[CH2:28][CH2:27][CH:26]([O:15][C:7]2[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:14]=[CH:13][C:8]=2[C:9]([O:11][CH3:12])=[O:10])[CH2:25][CH2:24]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 20777194Methyl 4-tert-butyl-2-hydroxybenzoate

Product 1

HCID 68532357methyl 4-(tert-butyl)-2-(1-Boc-piperidin-4-yloxy)benzoateYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-tert-butyl-2-hydroxybenzoate (2.04 g, 9.8 mmol) was placed in a dry 250 ml RBF along with 1-Boc-4-hydroxypiperidine (1.97 g, 9.8 mmol) and triphenylphosphine (2.57 g, 9.8 mmol). The solids were dissolved in 50 ml of dry THF; then the mixture was chilled on ice with stirring under a nitrogen atmosphere. Diisopropyl azodicarboxylate (DIAD) (1.98 g, 1.92 ml, 9.8 mmol) was added dropwise to the chilled solution over 20 min. The mixture was stirred a few minutes on ice, then allowed to warm to room temperature and left stirring overnight. The reaction mixture was concentrated in vacuo, partitioned between 200 ml each water and dichloromethane and the organic layer washed with brine, then dried over sodium sulfate and reconcentrated in vacuo. The yellow residue was dissolved in 70 ml of ether, then chilled (−10° C.) to precipitate most of the triphenylphosphine oxide. The mixture was filtered, reconcentrated and then purified on a Waters Prep 500 chromatograph (two cartridges, hexanes through 7:3 hexanes:EtOAc) to give the title product (2.41 g, 63%) as a colorless oil.

Workup

  1. temperaturethen the mixture was chilled on ice
  2. stirringThe mixture was stirred a few minutes on ice
  3. waitleft
  4. stirringstirring overnight
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. custompartitioned between 200 ml each water and dichloromethane
  7. washthe organic layer washed with brine
  8. dry with materialdried over sodium sulfate
  9. dissolutionThe yellow residue was dissolved in 70 ml of ether
  10. temperaturechilled (−10° C.)
  11. customto precipitate most of the triphenylphosphine oxide
  12. filtrationThe mixture was filtered
  13. custompurified on a Waters Prep 500 chromatograph (two cartridges, hexanes through 7:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-b7a2469b29e14100bd56151e8c8bf997
Source dataset
uspto-grants-2010_02
Patent number
US07666866B2

Reaction notes

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