Ethanaminium, N,N,N-triethyl-, fluoride (1:1) → HCID 57544655, compound

HRID 2355494Notes

Reaction equation

HRID 2355494 reaction equation
[Si](CC1CCC(C[C@H](NC(N2CCC[C@@H]([C@@](C3C=CC=C(Cl)C=3F)(O)CCCCOC)C2)=O)CN(C)C(=O)OCC[Si](C)(C)C)CC1)(C(C)(C)C)(C)C.[N+](CC)(CC)(CC)CC.[F-].[Cl:64][C:65]1[C:66]([F:100])=[C:67]([C@:71]([C@@H:79]2[CH2:84][CH2:83][CH2:82][N:81]([C:85]([NH:87][C@H:88]([CH2:97][NH:98][CH3:99])[CH2:89][C@H:90]3[CH2:95][CH2:94][C@H:93]([OH:96])[CH2:92][CH2:91]3)=[O:86])[CH2:80]2)([OH:78])[CH2:72][CH2:73][CH2:74][CH2:75][O:76][CH3:77])[CH:68]=[CH:69][CH:70]=1.ClC1C(F)=C([C@]([C@@H]2CCCN(C(N[C@H](CNC)C[C@H]3CC[C@@H](O)CC3)=O)C2)(O)CCCCOC)C=CC=1>CC#N>[Cl:64][C:65]1[C:66]([F:100])=[C:67]([C@:71]([C@@H:79]2[CH2:84][CH2:83][CH2:82][N:81]([C:85]([NH:87][C@H:88]([CH2:97][NH:98][CH3:99])[CH2:89][CH:90]3[CH2:91][CH2:92][CH:93]([OH:96])[CH2:94][CH2:95]3)=[O:86])[CH2:80]2)([OH:78])[CH2:72][CH2:73][CH2:74][CH2:75][O:76][CH3:77])[CH:68]=[CH:69][CH:70]=1

Participants

6

Reactant 4

HCID 69582Ethanaminium, N,N,N-triethyl-, fluoride (1:1)HCID 67189858HCID 67189858, compoundHCID 178484175HCID 178484175, compoundHCID 178484176HCID 178484176, compound

Product 1

HCID 57544655HCID 57544655, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2-(trimethylsilyl)ethyl (S)-3-(4-((tert-butyldimethylsilyl)methyl)cyclohexyl)-2-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)propyl(methyl)carbamate (79 mg, 0.0991 mmol) and Et4NF (36.9 mg, 0.248 mmol) in dry CH3CN (8 mL) was heated under reflux for 2 h. After the reaction was completed by analysis of HPLC, the mixture was concentrated in vacuo. The product was purified by preparative HPLC to give two isomeric compounds: (3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((2S)-1-(trans-4-hydroxycyclohexyl)-3-(methylamino)propan-2-yl)piperidine-1-carboxamide (16 mg, 0.0295 mmol) 1H NMR (400 MHz, CD3OD): 2.14 (m, 1H), 2.71 (s, 3H), 3.25 (s, 3H), 3.44-3.49 (m, 1H), 3.94-3.98 (m, 1H), 4.12 (m, 1H), 4.33-4.37 (m, 1H), 7.16-7.11 (t, 1H), 7.33-7.39 (m, 1H), 7.50-7.55 (m, 1H). MS (E/Z): 542 (M+H+) and (3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((2S)-1-(cis-4-hydroxycyclohexyl)-3-(methylamino)propan-2-yl)piperidine-1-carboxamide (10 mg, 0.0185 mmol) 1H NMR (400 MHz, CD3OD): 2.14 (m, 1H), 2.71 (s, 3H), 3.25 (s, 3H), 3.94-4.02 (m, 1H), 4.12 (m, 1H), 4.33-4.37 (m, 1H), 7.16-7.11 (t, 1H), 7.34-7.39 (m, 1H), 7.50-7.54 (m, 1H). MS (E/Z): 542 (M+H+).

Workup

  1. temperatureunder reflux for 2 h
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe product was purified by preparative HPLC
  4. customto give two isomeric compounds

Sources & evidence

ORD record
ord-f31cb3b5b4ae446da15fff4e629c2593
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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