Hydrochloric Acid → HCID 178445763, compound

HRID 2404101Notes

Reaction equation

HRID 2404101 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:23][CH:24]4[CH2:29][CH2:28][CH:27]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH2:25]4)[CH:19]=3)[CH:14]=2)[CH2:7]1)=[O:5])C.C(O)C.[OH-].[Na+].Cl>>[C:30]([C@H:27]1[CH2:28][CH2:29][C@H:24]([O:23][C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[CH:14]=[C:13]([CH2:12][N:8]2[CH2:9][CH2:10][CH2:11][C@@H:6]([C:4]([OH:5])=[O:3])[CH2:7]2)[CH:22]=[CH:21]3)[CH2:25][CH2:26]1)([CH3:33])([CH3:31])[CH3:32]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14798Sodium HydroxideHCID 66926766HCID 66926766, compound

Product 1

HCID 178445763HCID 178445763, compoundYield 45.8%

Procedure

(R)-1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-piperidine-3-carboxylic acid ethyl ester (363.4 mg, 0.8046 mmol) was dissolved in ethanol (5 mL, 80 mmol) then treated with 1 M aqueous sodium hydroxide (5 mL, 5 mmol). The mixture was stirred vigorously for 18 hours. pH was adjusted to 3-4 with 3 N HCl and reaction was then extracted three times with ethyl acetate. Organics were combined then dried over MgSO4, filtered and concentrated to dryness under reduced pressure. Ethyl ether was then added and a white precipitate formed which was removed via filtration to give a white solid that 86% pure by HPLC. The process was repeated two additional times to give the title compound as a white solid (156 mg, 44%). EDI-MS: 424.2 (M+H)+. 1H NMR (400 MHz, MeOD) δ=7.82 (s, 1H), 7.74-7.62 (m, 2H), 7.42 (d, J=2.3, 1H), 7.19 (d, J=2.3 Hz, 1H), 7.08 (d, J=2.5, 1H), 4.43-4.34 (m, 1H), 4.33-4.22 (m, 2H), 2.71 (br. s., 1H), 2.16 (d, J=2.0 Hz, 2H), 1.88-167 (m, 4H), 1.40-1.25 (m, 3H), 1.24-1.11 (m, 4H), 1.10-0.95 (m, 5H), 0.79 (s, 9H)

Workup

  1. extractionwas then extracted three times with ethyl acetate
  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 precipitate formed which
  7. customwas removed via filtration
  8. customto give a white solid that 86% pure by HPLC

Sources & evidence

ORD record
ord-2dc877d5b38e4d29b2310f0ed2539898
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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