Morpholine → tert-butyl 6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-carboxylate

HRID 1618697Notes

Reaction equation

HRID 1618697 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][C:8]3([CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:5]2=[N:6][CH:7]=1.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:26]1[CH2:27][CH2:28][N:23]([C:2]2[CH:3]=[C:4]3[N:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][C:8]4([CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]3=[N:6][CH:7]=2)[CH2:24][CH2:25]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 67284572tert-butyl 6'-bromo-2,3,5,6-tetrahydrospiro-[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-carboxylate

Product 1

HCID 67284807tert-butyl 6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure N using tert-butyl 6′-bromo-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]-1′(2′H)-carboxylate (12.0 g, 32.5 mmol), morpholine (3.11 mL, 35.7 mmol), Pd2dba3 (1.19 g, 1.30 mmol), XPhos (1.24 g, 0.08 mmol) and sodium tert-butoxide (6.25 g, 65.0 mmol) in toluene (200 mL) at 110° C. for 5 h. Purification by column chromatography (hexanes:EtOAC, 1:0 to 1:3 as eluent) gave tert-butyl 6′-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]-1′(2′H)-carboxylate. Mass Spectrum (ESI) m/e=376.2 (M+1).

Workup

  1. customPrepared
  2. customat 110° C.
  3. customfor 5 h
  4. customPurification by column chromatography (hexanes:EtOAC, 1:0 to 1:3 as eluent)

Sources & evidence

ORD record
ord-6a6148cf4e804bc6a959f2c18766de44
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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