Diisopropylethylamine → (2S,4S)-1-((S)-2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester

HRID 1481918Notes

Reaction equation

HRID 1481918 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[CH2:59]([O:66][C:67]([C@@H:69]1[CH2:73][C@H:72]([NH:74][C:75]([O:77][CH2:78][CH:79]2[C:91]3[CH:90]=[CH:89][CH:88]=[CH:87][C:86]=3[C:85]3[C:80]2=[CH:81][CH:82]=[CH:83][CH:84]=3)=[O:76])[CH2:71][NH:70]1)=[O:68])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1>CN(C=O)C>[CH2:59]([O:66][C:67]([C@@H:69]1[CH2:73][C@H:72]([NH:74][C:75]([O:77][CH2:78][CH:79]2[C:91]3[CH:90]=[CH:89][CH:88]=[CH:87][C:86]=3[C:85]3[C:80]2=[CH:81][CH:82]=[CH:83][CH:84]=3)=[O:76])[CH2:71][N:70]1[C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:68])[C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90220138(2S,4S)-4-(9H-Fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester trifluoroacetate

Product 1

HCID 118677402(2S,4S)-1-((S)-2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (Aldrich) (435 mg, 1.69 mmol) in DMF at 0° C. was added DIPEA (1.18 mL, 6.76 mmol) and HATU (674 mg, 1.77 mmol). After 30 minutes (2S,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester trifluoroacetate (0.94 g, 1.69 mmol) was added in one portion. The cooling bath was removed and the mixture stirred for 1 h, diluted with water, the resulting white precipitate collected, washed with water and air-dried to give (2S,4S)-1-((S)-2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester (1.07 g, 93%).

Workup

  1. customThe cooling bath was removed
  2. additiondiluted with water
  3. customthe resulting white precipitate collected
  4. washwashed with water
  5. customair-dried

Sources & evidence

ORD record
ord-9ed1126acb5e4c8d85454db2acfc0951
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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