Diisopropylethylamine → ethyl 5-[4-[[N-[N-[(9-fluorenyl)methoxycarbonyl]-L-leucyl]-N-[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propyl]amino]methyl]-3,5-dimethoxyphenoxy]valerate

HRID 850869Notes

Reaction equation

HRID 850869 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:24](O)=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.[F:60][C:61]([F:92])([F:91])[CH2:62][CH:63]([NH:69][CH2:70][C:71]1[C:86]([O:87][CH3:88])=[CH:85][C:74]([O:75][CH2:76][CH2:77][CH2:78][CH2:79][C:80]([O:82][CH2:83][CH3:84])=[O:81])=[CH:73][C:72]=1[O:89][CH3:90])[CH:64]([O:67][CH3:68])[O:65][CH3:66].C(N(C(C)C)CC)(C)C>ClCCl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:24]([N:69]([CH2:70][C:71]3[C:72]([O:89][CH3:90])=[CH:73][C:74]([O:75][CH2:76][CH2:77][CH2:78][CH2:79][C:80]([O:82][CH2:83][CH3:84])=[O:81])=[CH:85][C:86]=3[O:87][CH3:88])[CH:63]([CH:64]([O:65][CH3:66])[O:67][CH3:68])[CH2:62][C:61]([F:91])([F:92])[F:60])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1549133Fmoc-leucineHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 22619160ethyl 5-[4-[[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propylamino]methyl]-3,5-dimethoxyphenoxy]valerate

Product 1

HCID 22942077ethyl 5-[4-[[N-[N-[(9-fluorenyl)methoxycarbonyl]-L-leucyl]-N-[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propyl]amino]methyl]-3,5-dimethoxyphenoxy]valerateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 6.6 g (18.7 mmol) of N-[(9-fluorenyl)-methoxycarbonyl]-L-leucine and 9.7 g (18.7 mmol) of 7-azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate in 50 ml of anhydrous dichloromethane was stirred at room temperature for 15 minutes. To this mixture were then added 6.0 g (12.4 mmol) of ethyl 5-[4-[[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propylamino]methyl]-3,5-dimethoxyphenoxy]valerate and 4.3 ml of (24.8 mmol) diisopropylethylamine. After stirring overnight at 25° C. the mixture was diluted with dichloromethane and washed in sequence with water, 10% citric acid solution, saturated sodium hydrogen carbonate solution and saturated sodium chloride solution, then dried over anhydrous magnesium sulphate and filtered. The solvent was removed by evaporation and the residue was chromatographed on silica gel using 30% ethyl acetate in hexane for the elution. There were obtained 8.06 g of ethyl 5-[4-[[N-[N-[(9-fluorenyl)methoxycarbonyl]-L-leucyl]-N-[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propyl]amino]methyl]-3,5-dimethoxyphenoxy]valerate; MS: m/e 839.4 [M+Na], 855.3 [M+K].

Workup

  1. washwashed in sequence with water, 10% citric acid solution, saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
  2. dry with materialdried over anhydrous magnesium sulphate
  3. filtrationfiltered
  4. customThe solvent was removed by evaporation
  5. customthe residue was chromatographed on silica gel using 30% ethyl acetate in hexane for the elution

Sources & evidence

ORD record
ord-4d89f8d23be94fe09dbb418f48e8a096
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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