Hydrochloric Acid → 3-{1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-2,2,2-trifluoro-ethylamino}-propionic acid

HRID 713975Notes

Reaction equation

HRID 713975 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][CH2:5][NH:6][CH:7]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH:23]3[CH2:28][CH2:27][CH:26]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:25][CH2:24]3)[CH:18]=2)[CH:13]=1)[C:8]([F:11])([F:10])[F:9].C(O)C.[OH-].[Na+].O.Cl>>[C:29]([CH:26]1[CH2:27][CH2:28][CH:23]([O:22][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[CH:13]=[C:12]([CH:7]([NH:6][CH2:5][CH2:4][C:3]([OH:33])=[O:2])[C:8]([F:11])([F:9])[F:10])[CH:21]=[CH:20]3)[CH2:24][CH2:25]1)([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 962WaterHCID 14798Sodium HydroxideHCID 669267543-(1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-2,2,2-trifluoro-ethylamino)-propionic acid methyl ester

Product 1

HCID 669265503-{1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-2,2,2-trifluoro-ethylamino}-propionic acid

Procedure

3-{1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-2,2,2-trifluoro-ethylamino}-propionic acid methyl ester (164 mg, 0.352 mmol) was dissolved in Ethanol (2 mL, 40 mmol) then treated with 1 M of sodium hydroxide in Water (2 mL, 2 mmol). The mixture was stirred vigorously for 1 hour. pH was adjust to 3-4 with 6 N HCl and reaction was then extracted three times with EtOAc. Organics were combined then dried over MgSO4, filtered and concentrated to dryness under reduced pressure. Ethyl ether was then added and a white ppt formed. The ppt. was removed via filtration to give a white solid that 99% pure by NMR and HPLC-traces of ethanol remain. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.83 (s, 9H) 0.93-1.10 (m, 1H) 1.11-1.27 (m, 2H) 1.27-1.42 (m, 2H) 1.73-1.89 (m, 2H) 2.19 (d, J=10.29 Hz, 2H) 2.67 (t, J=6.53 Hz, 2H) 3.03-3.18 (m, 2H) 4.22-4.37 (m, 1H) 5.33-5.51 (m, 1H) 7.13 (dd, J=8.91, 2.38 Hz, 1H) 7.21-7.29 (m, 1H) 7.46 (d, J=8.78 Hz, 1H) 7.76 (d, J=9.04 Hz, 1H) 7.85 (d, J=8.78 Hz, 1H) 7.93 (s, 1H).

Workup

  1. extractionwas then extracted three times with EtOAc
  2. dry with materialOrganics were combined then dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure
  5. additionEthyl ether was then added
  6. customa white ppt formed
  7. customwas removed via filtration
  8. customto give a white solid that 99% pure by NMR and HPLC-traces of ethanol

Sources & evidence

ORD record
ord-b8862f1c08154846b94aad3d69828248
Source dataset
uspto-grants-2015_11
Patent number
US09186367B2

Reaction notes

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