Diisopropylethylamine → (S)-(1-(2-(tert-butoxycarbonyl)amino-3-hydroxypropanoyl)-4-(2-chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate

HRID 655953Notes

Reaction equation

HRID 655953 reaction equation
[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=O)[CH2:3][OH:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:39][C:40]([F:70])([F:69])[C:41]1[CH:46]=[CH:45][C:44]([NH:47][C:48](=[O:68])[O:49][CH2:50][C:51]2([C:57](=[O:67])[NH:58][CH2:59][C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[Cl:66])[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)=[CH:43][CH:42]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:70][C:40]([F:39])([F:69])[C:41]1[CH:46]=[CH:45][C:44]([NH:47][C:48](=[O:68])[O:49][CH2:50][C:51]2([C:57](=[O:67])[NH:58][CH2:59][C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[Cl:66])[CH2:52][CH2:53][N:54]([C:5](=[O:7])[C@@H:2]([NH:1][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][OH:4])[CH2:55][CH2:56]2)=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59778560(4-(2-Chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate

Product 1

HCID 59778634(S)-(1-(2-(tert-butoxycarbonyl)amino-3-hydroxypropanoyl)-4-(2-chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamateYield 56.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Boc-Ser-OH (162 mg, 0.79 mmol, 2 equiv.) in DMF (2 mL) were added HATU (300 mg, 0.79 mmol, 2 equiv.), followed by addition of (4-(2-chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate (200 mg, 0.39 mmol, 1 equiv.) and DIEA (140 μL, 0.79 mmol, 2 equiv.). The reaction mixture was stirred overnight and purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-(1-(2-(tert-butoxycarbonyl)amino-3-hydroxypropanoyl)-4-(2-chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate (145 mg, 56%). LRMS (M+H+-Boc) m/z 557.1.

Workup

  1. custompurified on RP-HPLC
  2. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-844e0f97ac974226939344285058446c
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Reaction notes

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