Lithium Hydroxide → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(tetrahydropyran-2-carbonyl)amino]pentanoic Acid

HRID 1397642Notes

Reaction equation

HRID 1397642 reaction equation
C([O:3][C:4](=[O:24])[C@H:5]([OH:23])[CH2:6][C@H:7]([NH2:22])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)C.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[C:31](O)=[O:32].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.[Li+].[OH-]>CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([CH2:8][C@@H:7]([NH:22][C:31]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)=[O:32])[CH2:6][C@@H:5]([OH:23])[C:4]([OH:3])=[O:24])=[CH:10][CH:11]=2)[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10964532Oxane-2-carboxylic acidHCID 86682253(2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester

Product 1

HCID 90387417(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(tetrahydropyran-2-carbonyl)amino]pentanoic AcidYield 52.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R,4R)-4-Amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (50 mg, 144 μmol) was added to a solution of tetrahydro-pyran-2-carboxylic acid (1.2 eq., 165 mmol) and HATU (71.1 mg, 187 mmol) in DMF (250 μL), followed by the addition of DIPEA (75 μL, 431 mmol). The resulting mixture was stirred at room temperature for 1 hour. 10 M aqueous LiOH (115 μL, 1.2 mmol) was added and the mixture was stirred for an additional 1 hour. The mixture was washed with DCM (1 mL) and the aqueous layer was acidified with concentrated HCl (250 μL) and extracted with DCM (2×1 mL). The DCM extracts were combined and concentrated in vacuo, and the resulting crude liquid was purified by reverse phase preparative HPLC to yield the title compound (32.6 mg). MS m/z [M+H]+ calc'd for C23H26ClNO5, 432.15; found 432.2.

Workup

  1. stirringthe mixture was stirred for an additional 1 hour
  2. washThe mixture was washed with DCM (1 mL)
  3. extractionextracted with DCM (2×1 mL)
  4. concentrationconcentrated in vacuo
  5. customthe resulting crude liquid was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-c890854eebd44ad3a132ebc994c3152d
Source dataset
uspto-grants-2014_12
Patent number
US08901169B2

Reaction notes

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