Potassium tert-butoxide → 2-[2-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-8-oxa-2-aza-spiro[4.5]decan-1-one

HRID 2401131Notes

Reaction equation

HRID 2401131 reaction equation
C[O:2][C:3]([C:5]1([CH2:11][CH2:12][NH:13][C:14]2[C:15]([CH3:31])=[N:16][C:17]([N:20]3[CH2:24][CH2:23][C@H:22]([N:25]4[CH2:29][CH2:28][CH2:27][C@@H:26]4[CH3:30])[CH2:21]3)=[CH:18][CH:19]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=O.CC(C)([O-])C.[K+]>C1COCC1.C(OCC)(=O)C>[CH3:31][C:15]1[C:14]([N:13]2[CH2:12][CH2:11][C:5]3([CH2:6][CH2:7][O:8][CH2:9][CH2:10]3)[C:3]2=[O:2])=[CH:19][CH:18]=[C:17]([N:20]2[CH2:24][CH2:23][C@H:22]([N:25]3[CH2:29][CH2:28][CH2:27][C@@H:26]3[CH3:30])[CH2:21]2)[N:16]=1

Participants

5

Reactant 2

HCID 23665647Potassium tert-butoxide3×HCID 712804254-{2-[2-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

Product 1

HCID 545910722-[2-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-8-oxa-2-aza-spiro[4.5]decan-1-oneYield 22%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-{2-[2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester (0.034 g, 0.079 mmol) in THF (10 mL) was added a solution of potassium t-butoxide (1M in THF) (0.2 mL), and allowed to stir at room temperature. After 3 hours additional potassium t-butoxide (0.4 mL) was added and reaction mixture stirred at room temperature for 16 hours. More potassium t-butoxide (0.2 mL) was added and stirred at room temperature for 4 hours, then heated to 50° C. for 3 hours. Reaction mixture was cooled to room temperature then diluted with ethyl acetate (10 mL), quenched with brine (2 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). Combined organics were washed with brine, dried over Na2SO4, and concentrated under vacuum. Purification over silica gel eluting with methanol in dichloromethane (0-10%) afforded 0.0068 g (22%) of title compound.

Workup

  1. customreaction mixture
  2. stirringstirred at room temperature for 16 hours
  3. stirringstirred at room temperature for 4 hours
  4. temperatureheated to 50° C. for 3 hours
  5. customReaction mixture
  6. temperaturewas cooled to room temperature
  7. customquenched with brine (2 mL)
  8. extractionAqueous layer was extracted with ethyl acetate (2×10 mL)
  9. washCombined organics were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under vacuum
  12. customPurification over silica gel eluting with methanol in dichloromethane (0-10%)

Sources & evidence

ORD record
ord-80b90e2fcf6e4c70a06e236a14cf3143
Source dataset
uspto-grants-2014_08
Patent number
US08796278B2

Reaction notes

Loading…