N-methyl-2-pyrrolidone → HCID 86661653, compound

HRID 2041122Notes

Reaction equation

HRID 2041122 reaction equation
Br[C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[OH:19].[CH3:20][N:21]1C(=O)CCC1>>[C:20]([C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[OH:19])#[N:21]

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 57655992HCID 57655992, compound

Product 1

HCID 86661653HCID 86661653, compoundYield 86%

Conditions

Temperature
150 °C

Procedure

Add copper nitrile (2.6 g, 28 mmol) to a solution of 7-bromo-6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.4 g, 7.0 mmol) in anhydrous NMP (45 mL), degas and purge with nitrogen and heat to 150° C. for 18 h. Allow the reaction mixture to cool to ambient temperature and then dilute with EtOAc/heptane (2:1) and filter through a silica pad. Dilute the filtrate with water, and extract the aqueous phase twice with EtOAc. Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with EtOAc/heptane (1:4 to 1:1) to obtain the desired intermediate as an orange oil (1.7 g, 86%). MS (ES−) m/z: 283 (M−H)−.

Workup

  1. customdegas
  2. custompurge with nitrogen
  3. temperatureto cool to ambient temperature
  4. additiondilute with EtOAc/heptane (2:1)
  5. filtrationfilter through a silica pad
  6. additionDilute the filtrate with water
  7. extractionextract the aqueous phase twice with EtOAc
  8. dry with materialDry the combined organic extracts over MgSO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify by chromatography on silica gel eluting with EtOAc/heptane (1:4 to 1:1)

Sources & evidence

ORD record
ord-02d6291f688a40da9138d7d840ed49aa
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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