Triethylamine → HCID 57845344, compound

HRID 734383Notes

Reaction equation

HRID 734383 reaction equation
[F:1][C@H:2]1[C@@H:7]([CH2:8]C(O)=O)[CH2:6][CH2:5][N:4]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[O:13])[CH2:3]1.C([N:25](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1>[NH2:25][CH2:8][C@H:7]1[CH2:6][CH2:5][N:4]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[O:13])[CH2:3][C@H:2]1[F:1]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 57845345HCID 57845345, compound

Product 1

HCID 57845344HCID 57845344, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of crude acid (±)-((cis)-3-fluoro-1-{[(4-methylbenzyl)oxy]carbonyl}piperidin-4-yl)acetic acid (9.1 g, 29.4 mmol) in toluene (80 mL) was added triethylamine (10.2 mL, 73.5 mmol) and diphenylphosphoryl azide (9.52 mL, 44.1 mmol). The reaction mixture was heated to 70° C. and stirred for 20 min. A mixture of dioxane (80 mL) and 1 M NaOH (80 mL) was added and the reaction mixture was cooled to RT. The reaction mixture was concentrated to remove the dioxane and extracted with EtOAc three times, dried over Na2SO4, filtered and concentrated. The residue was suspended in CH2Cl2, stirred for 30 min, and the white preciptate filtered off. The filtrate was concentrated to give crude product (7.5 g) as a yellow oil, used directly in the next step. An analytical sample was purified by silica gel chromatography (gradient elution: CH2Cl2 to 80:20:2 CH2Cl2:MeOH:NH4OH) for characterization:

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was cooled to RT
  3. concentrationThe reaction mixture was concentrated
  4. customto remove the dioxane
  5. extractionextracted with EtOAc three times
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. stirringstirred for 30 min
  10. filtrationthe white preciptate filtered off
  11. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4fa7ef47e3844e8a957c1b6a4be4f05c
Source dataset
uspto-grants-2009_09
Patent number
US07592360B2

Reaction notes

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