Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 1-(2-hydroxy-2-phenyl-3,3,3-trifluoropropanoyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide

HRID 1058290Notes

Reaction equation

HRID 1058290 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=1[CH2:12][NH:13][C:14](=[O:20])[C@@H:15]1[CH2:19][CH2:18][CH2:17][NH:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na].[C:27]1([C:33]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:34](O)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:41][C:33]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:37]([F:38])([F:39])[F:40])[C:34]([N:16]1[CH2:17][CH2:18][CH2:19][C@H:15]1[C:14]([NH:13][CH2:12][C:11]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:10]=1[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:20])=[O:35]

Participants

6

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5360545SodiumHCID 98559433,3,3-Trifluoro-2-hydroxy-2-phenylpropanoic acidHCID 11428605L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amide

Product 1

HCID 699388101-(2-hydroxy-2-phenyl-3,3,3-trifluoropropanoyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amide (200 mg, 0.544 mmol) and the sodium salt of 2-phenyl-2-hydroxy-3,3,3-trifluoropropanoic acid from the previous step (144 mg, 0.652 mmol) in DMF (5 mL) at ambient temperature under nitrogen atmosphere was added BOP reagent (288 mg, 0.652 mmol). The mixture was stirred at ambient temperature for 72 h. The solvent was removed under reduced pressure and the residue was purified by preparative reverse phase HPLC using a gradient of 95:5 to 0:100 (water:CH3CN, 0.1% TFA) over 60 min with a flow rate of 60 mL/min. After concentration of desired fractions in vacuo the two diastereomers of 1-(2-hydroxy-2-phenyl-3,3,3-trifluoropropanoyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide were obtained as amorphous solids (isomer 1 (more polar) 8.5 mg; HPLC RT=3.70 min, method A; LC-MS m/z=570.1; isomer 2 (less polar) 70 mg; HPLC RT=3.57 min, method A; LC-MS m/z=570.1).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by preparative reverse phase HPLC
  3. customover 60 min

Sources & evidence

ORD record
ord-97fc02c9a058450dbf17737699aa8e8f
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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