Sodium Iodide → Methyl 2-(2-methoxy-4-(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-ylcarbonyl)phenoxy)acetate

HRID 2204244Notes

Reaction equation

HRID 2204244 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3([O:20][C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[N:17]4[CH:25]=[CH:26][CH:27]=[C:16]34)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[O:28][CH3:29].[I-].[Na+].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:39][C:40]([O:42][CH3:43])=[O:41]>ClCCCl>[CH3:29][O:28][C:3]1[CH:4]=[C:5]([C:8]([N:10]2[CH2:11][CH2:12][C:13]3([O:20][C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[N:17]4[CH:25]=[CH:26][CH:27]=[C:16]34)[CH2:14][CH2:15]2)=[O:9])[CH:6]=[CH:7][C:2]=1[O:1][CH2:39][C:40]([O:42][CH3:43])=[O:41]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 60984Methyl bromoacetate2×HCID 58551823(4-Hydroxy-3-methoxyphenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)methanone

Product 1

HCID 58550733Methyl 2-(2-methoxy-4-(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-ylcarbonyl)phenoxy)acetateYield 59.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

To (4-hydroxy-3-methoxyphenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone (200 mg, 0.512 mmol), sodium iodide (38.4 mg, 0.256 mmol), Cs2CO3 (334 mg, 1.03 mmol), and DCE (5.0 mL) was added methyl 2-bromoacetate (49 μL, 0.51 mmol). The mixture was stirred at 60° C. for 18 h. Additional methyl 2-bromoacetate (1.0 mmol) was added and the mixture was heated for 3 h at 60° C. The mixture was cooled and then filtered. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography on silica gel (0-30% ethyl acetate/DCM) to yield methyl 2-(2-methoxy-4-(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-ylcarbonyl)phenoxy)acetate (140 mg, 59%). ESI-MS m/z calc. 462.2, found 463.5 (M+1)+; Retention time: 2.68 minutes (4 min run).

Workup

  1. temperaturethe mixture was heated for 3 h at 60° C
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. customThe solvent was evaporated under reduced pressure
  5. customthe crude product was purified by column chromatography on silica gel (0-30% ethyl acetate/DCM)

Sources & evidence

ORD record
ord-9fed215eaed646b985560df0f3a2043e
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

Loading…