Hydrochloric Acid → 1-methyl-1H-spiro[chromeno[4,3-b]pyrrole-4,4'-piperidine]

HRID 2204122Notes

Reaction equation

HRID 2204122 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[OH:13].O=[C:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.O.CC1C=CC(S(O)(=O)=O)=CC=1.ClC(Cl)C.Cl>>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]2[C:15]3([O:13][C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=4[C:3]1=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 63651,1-DichloroethaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 220904482-(1-Methyl-1H-pyrrol-2-yl)phenol

Product 1

HCID 585518401-methyl-1H-spiro[chromeno[4,3-b]pyrrole-4,4'-piperidine]

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(1-methylpyrrol-2-yl)phenol (1.20 g, 6.90 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (1.38 g, 6.93 mmol), 4-methylbenzenesulfonic acid hydrate (264 mg, 1.39 mmol), and dichloroethane (24 mL) was heated at 80° C. for 2 h. To the mixture was added HCl (1.7 mL of 4.0 M, 6.9 mmol) and the mixture was allowed to stir at 50° C. for 1 h. The mixture was cooled to 25° C. and was concentrated in vacuo. The residue was taken up in dichloromethane and was washed with saturated aqueous NaHCO3. The organic layer was dried over sodium sulfate and concentrated. Column chromatography (0-100% ethyl acetate/hexanes) on the residue gave 1-methyl-1H-spiro[chromeno[4,3-b]pyrrole-4,4′-piperidine]. ESI-MS m/z calc. 254.3, found 255.2 (M+1)+; Retention time: 1.51 minutes (3 min run).

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationwas concentrated in vacuo
  3. washwas washed with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-dc305335409844eb8b4b06b6fb052359
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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