Phosphate → HCID 72950366, compound

HRID 1526786Notes

Reaction equation

HRID 1526786 reaction equation
Cl.C([O:4][C:5](=[O:23])[CH2:6][CH:7]([NH2:22])[C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]([OH:21])([CH3:20])[CH3:19])[CH:9]=1)C.[OH-].[Na+].OP([O-])(O)=O.[K+].P([O-])([O-])([O-])=O>O.C(OC)(C)(C)C>[NH2:22][C@H:7]([C:8]1[CH:13]=[C:12]([C:14]([F:16])([F:17])[F:15])[CH:11]=[C:10]([C:18]([OH:21])([CH3:19])[CH3:20])[CH:9]=1)[CH2:6][C:5]([OH:23])=[O:4]

Participants

7

Reactant 4

HCID 1061PhosphateHCID 14798Sodium HydroxideHCID 516951Monobasic potassium phosphateHCID 89955411HCID 89955411, compound

Product 1

HCID 72950366HCID 72950366, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A suspension of racemic ethyl 3-amino-3-(3-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)phenyl)propanoate hydrochloride (Example J) (540.4 mg, 1.52 mmol) in water (2.0 mL) was basified with 2.5 N NaOH solution (pH 12) by drop wise addition to give a dirty pink oily residue. The pH of the aqueous phase was adjusted to pH 8.20 by the addition of 50 mom KH2PO4 solution (40.0 mL). Amano Lipase PS (607.6 mg) was added to the above suspension and the reaction mixture was stirred at room temperature for 63 h to give a pale pink suspension. The reaction mixture was diluted with methyl t-butyl ether (MTBE) (50 mL) and the reaction mixture was stirred at room temperature for 30 min. After 30 min, the organic layer containing the (R)-ester was separated. Evaporation of the aqueous layer in vacuo afforded a cream gummy solid containing the (S)-acid as well as Amano Lipase and Phosphate buffer salt. LC-MS analysis of the crude residue shows the desired (S)-acid's mass: m/z 292 (M+H), m/z 314 (M+Na), and m/z 274 (M+H−H2O); Calcd for C13H16F3NO3: 291.27. The crude product was purified by reverse-phase HPLC with a gradient 10-40% CH3CN in water containing 0.05% TFA to give the desired product, after lyophilization, as a colorless lyophilized solid (324 mg) (TFA salt).

Workup

  1. customto give a dirty pink oily residue
  2. additionAmano Lipase PS (607.6 mg) was added to the above suspension
  3. customto give a pale pink suspension
  4. stirringthe reaction mixture was stirred at room temperature for 30 min
  5. waitAfter 30 min
  6. customwas separated
  7. customEvaporation of the aqueous layer in vacuo
  8. customafforded a cream gummy solid
  9. customThe crude product was purified by reverse-phase HPLC with a gradient 10-40% CH3CN in water containing 0.05% TFA

Sources & evidence

ORD record
ord-12c572cb54694b0791bec890a31c7428
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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