Hydrochloric Acid → rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide

HRID 1806921Notes

Reaction equation

HRID 1806921 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]([C:18]([CH3:47])([CH3:46])[CH2:19][CH:20]1[NH:24][CH:23]([C:25]([OH:27])=O)[CH:22]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[F:35])[C:21]1([C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=1[F:45])[C:36]#[N:37])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CC1(C)[O:53][C@@H:52]([CH2:54][CH2:55][NH2:56])[CH2:51][O:50]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.O1CCCC1>[OH:53][C@H:52]([CH2:51][OH:50])[CH2:54][CH2:55][NH:56][C:25]([CH:23]1[CH:22]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[F:35])[C:21]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=2[F:45])([C:36]#[N:37])[CH:20]([CH2:19][C:18]([C:16]([O:15][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:17])([CH3:47])[CH3:46])[NH:24]1)=[O:27]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 282937772-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethan-1-amineHCID 86640381rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid trifluoroacetic acid

Product 1

HCID 86640382rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amideYield 22.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a manner similar to the method described in Examples 42c and 42d, rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 103c (0.94 g, 1.34 mmol) was reacted with 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.58 g, 4.0 mmol), HATU (0.92 g, 2.41 mmol) and iPr2NEt (1.17 mL, 6.7 mmol) in CH2Cl2 at room temperature for 20 h, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.2 g, 22%).

Sources & evidence

ORD record
ord-4fa5b030276b4543bb839ded70f2d1db
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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