Diisopropylethylamine → 2-{3-[(1R,2R)-2-butoxycarbonyl-1-(2-chloro-benzyl)-2-hydroxy-ethylcarbamoyl]-propyl}-benzoic acid

HRID 2361112Notes

Reaction equation

HRID 2361112 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])([OH:3])=O.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.[CH2:49]([O:53][C:54](=[O:67])[C@H:55]([OH:66])[C@H:56]([NH2:65])[CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=1[Cl:64])[CH2:50][CH2:51][CH3:52]>C(Cl)Cl>[CH2:49]([O:53][C:54]([C@H:55]([OH:66])[C@H:56]([NH:65][C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])=[O:3])[CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=1[Cl:64])=[O:67])[CH2:50][CH2:51][CH3:52]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 124220832-(3-Carboxypropyl)benzoic acidHCID 71073857(2R,3R)-3-amino-4-(2-chloro-phenyl)-2-hydroxy-butyric Acid Butyl Ester

Product 1

HCID 710736552-{3-[(1R,2R)-2-butoxycarbonyl-1-(2-chloro-benzyl)-2-hydroxy-ethylcarbamoyl]-propyl}-benzoic acidYield 19.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3-Carboxy-propyl)benzoic acid (335 mg, 1.6 mmol, 1.0 eq.) was combined with DIPEA (897 μL, 3.2 eq.) and HATU (0.612 g, 1.61 mmol, 1.0 eq.) in DCM (40 mL). The resulting mixture was stirred for 10 minutes and (2R,3R)-3-amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid butyl ester (HCl salt, 519 mg, 1.6 mmol, 1.0 eq.) was added. The reaction was quenched after 1 hour by adding saturated NH4Cl and the product was extracted with DCM, dried and evaporated. The product was dissolved into AcOH (5 mL) and purified using preparative HPLC. The clean fractions were combined and lyophilized to yield 2-{3-[(1R,2R)-2-butoxycarbonyl-1-(2-chloro-benzyl)-2-hydroxy-ethylcarbamoyl]-propyl}-benzoic acid (150 mg).

Workup

  1. customThe reaction was quenched after 1 hour
  2. additionby adding saturated NH4Cl
  3. extractionthe product was extracted with DCM
  4. customdried
  5. customevaporated
  6. dissolutionThe product was dissolved into AcOH (5 mL)
  7. custompurified

Sources & evidence

ORD record
ord-763a5c77c81f43099cf7c2675384ecd3
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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