Potassium Iodide → HCID 59837421, compound

HRID 272931Notes

Reaction equation

HRID 272931 reaction equation
BrCCCOC1C=CC(C2(C#[N:19])CCCCC2)=CC=1.Cl[CH2:21][CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2([C:37]#[N:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].[I-].[K+].[CH3:47][O:48][CH2:49][C@H:50]1[CH2:54][CH2:53][CH2:52][NH:51]1>CN1C(=O)CCC1>[NH3:19].[CH3:47][O:48][CH2:49][C@H:50]1[CH2:54][CH2:53][CH2:52][N:51]1[CH2:21][CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2([C:37]#[N:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:27][CH:26]=1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 23091704HCID 23091704, compoundHCID 598375041-[4-(3-Bromo-propoxy)-phenyl]-cyclohexanecarbonitrile

Product 2

HCID 222AmmoniaHCID 59837421HCID 59837421, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
75 °C

Procedure

A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (2.00 g, 7.20 mmol), Cs2CO3 (2.58 g, 7.20 mmol), potassium iodide (0.20 g, 1.20 mmol) and (R)-(−)-2-(methoxymethyl)pyrrolidine (1.07 mL, 8.60 mmol) in NMP (20 mL) was heated to 75° C. overnight. The reaction mixture was cooled to ambient temperature, concentrated in vacuo, and quenched by adding water (30 mL). The crude product was extracted with ethyl acetate (30×mL) and the organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 100:0:0 to 90:10:1 to give the title compound as a brown oil (1.39 g, 54%). 1H NMR (400 MHz, CDCl3) δ 7.38 (d, 2H), 6.70 (d, 2H), 4.02 (t, 2H), 3.46-3.38 (m, 1H), 3.36-3.28 (m, 3H), 3.24-3.16 (m, 1H), 3.12-3.04 (m, 1H), 2.72-2.58 (m, 1H), 2.52-2.44 (m, 1H), 2.30-2.20 (m, 1H), 2.18-2.06 (m, 2H), 1.98 (pentet, 2H), 1.92-1.60 (m, 12H), 1.36-1.18 (m, 1H); HRMS (ESI+) 357.2537 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customquenched
  4. additionby adding water (30 mL)
  5. extractionThe crude product was extracted with ethyl acetate (30×mL)
  6. dry with materialthe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe compound was purified by column chromatography on Biotage® silica gel
  10. washeluting with dichloromethane

Sources & evidence

ORD record
ord-439af9c4efb94e9586d82a556bc5af98
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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