18-Crown-6 → tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)piperidine-1-carboxylate

HRID 527988Notes

Reaction equation

HRID 527988 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[C:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[C:6]([Cl:23])[N:5]=[CH:4][N:3]=1.CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:23][C:6]1[C:7]2[CH:8]=[C:9]([CH:10]3[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:14][CH2:15]3)[NH:1][C:2]=2[N:3]=[CH:4][N:5]=1

Participants

6

Reactant 3

HCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 90418839Tert-butyl 4-((4-amino-6-chloropyrimidin-5-yl)ethynyl)piperidine-1-carboxylate

Product 1

HCID 90418107tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of Example 1B (250 mg, 0.74 mmol), in toluene (5 mL), was added potassium tert-butoxide (249 mg, 2.22 mmol) followed by 18-crown-6 (15 mg, 0.057 mmol) and the mixture was heated under nitrogen at 65° C. for 12 hours. The mixture was cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, concentrated and purified by column chromatography (silica gel, 40% ethyl acetate in hexane) to afford the title compound. LCMS: 337.1 (M+1)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography (silica gel, 40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7e65c9b42da0409e8ac89b9dd68e4146
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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