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 362128

Reaction equation

HRID 362128 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×

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 250C 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 andfiltered. 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. customThe solvent was removed by evaporation
  4. customthe residue was chromatographed on silica gel using 30% ethyl acetate in hexane for the elution

Sources & evidence

ORD record
ord-8439c3e448cb43f5a49be84f56c3ea70
Source dataset
uspto-grants-1999_02
Patent number
US05866684

Linked notes

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