Diazald → HCID 54284657, compound

HRID 1857608Notes

Reaction equation

HRID 1857608 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.[N+:25](=[CH2:27])=[N-:26].CC1C=CC(S(N(N=O)C)(=O)=O)=CC=1.[OH-].[K+].C(OCCOCCO)C>O1CCCC1.C(OCC)C.O.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14](=[O:16])[CH:27]=[N+:25]=[N-:26])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

11

Reactant 6

HCID 6628Diazald2×HCID 8146Diethylene Glycol Monoethyl EtherHCID 9550DiazomethaneHCID 14797Potassium HydroxideHCID 62365Isobutyl chloroformateHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acid

Product 1

HCID 54284657HCID 54284657, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent4×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (S)-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (3.0 g in a mixture of 26 mL dry tetrahydrofuran and 26 mL dry diethyl ether) at -10° C. was added 1.91 mL of triethylamine followed by the dropwise addition of 1.78 mL isobutyl chloroformate. The reaction was stirred at -10° C. for 30 minutes then warmed to 0° C. Over the next hour, 26 mL of a solution of diazomethane in diethyl ether was added (prepared from: 8.0 g Diazald® in 70 mL diethyl ether; 4 g potassium hydroxide; 20 mL 2-(2-ethoxyethoxy)ethanol; 6 mL water and 12 mL diethyl ether using a mini Diazald Kit) and the mixture allowed to stir at room temperature for an additional 2 hours. At this time the reaction was quenched by the addition of 3 mL acetic acid at 0° C. This was then diluted with 100 mL water and 100 mL diethyl ether, the layers separated and the aqueous portion extracted with (2×75 mL) diethyl ether. The combined organics were washed with water (75 mL), saturated sodium bicarbonate (2×75 mL) and brine (75 mL) then dried over magnesium sulfate. Removal of the solvent in vacuo and purification of the residue by flash chromatography on silica gel (hexane:ethyl acetate, 8:2) gave the title compound, 2.99 g.

Workup

  1. temperaturethen warmed to 0° C
  2. stirringto stir at room temperature for an additional 2 hours
  3. customAt this time the reaction was quenched by the addition of 3 mL acetic acid at 0° C
  4. additionThis was then diluted with 100 mL water and 100 mL diethyl ether
  5. customthe layers separated
  6. extractionthe aqueous portion extracted with (2×75 mL) diethyl ether
  7. washThe combined organics were washed with water (75 mL), saturated sodium bicarbonate (2×75 mL) and brine (75 mL)
  8. dry with materialthen dried over magnesium sulfate
  9. customRemoval of the solvent
  10. customin vacuo and purification of the residue by flash chromatography on silica gel (hexane:ethyl acetate, 8:2)

Sources & evidence

ORD record
ord-6f9f4326fe9849de8911368a88e9aa6a
Source dataset
uspto-grants-2000_11
Patent number
US06147088

Reaction notes

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