Sodium Hydroxide → (S)-2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetic acid

HRID 514010Notes

Reaction equation

HRID 514010 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C.C(OCC)(=O)C>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86691533(S)-ethyl 2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetate

Product 1

HCID 56601711(S)-2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetic acidYield 59.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of above intermediate (S)-ethyl 2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetate (8 mg, 0.021 mmol, 1 eq.) in ethanol (1.5 mL) and 1 N sodium hydroxide (0.42 mL, 20 eq.) was heated at 60° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The aqueous layer was back-extracted with ethyl acetate and the combined organic layer was dried (MgSO4), filtered, concentrated and purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). Product lyophilized to give 8 as a white powder (4.4 mg). Analytical HPLC (Gemini, 2-98% ACN/H2O+0.05% TFA, 10 minutes run): tR (min)=6.10. 1H-NMR: 400 MHz, (CD3OD) δ: 7.83 (m, 1H), 7.70 (m, 1H), 7.54 (m, 1H), 7.40 (m, 2H), 5.82, 5.62 (s, s, 1H), 2.58 (m, 3H), 2.62-2.16 (m, 4H), 1.92-1.80 (m, 4H), 1.03 (m, 9H). LCMS-ESI31 (m/z): [M−H]− calcd for C23H27O3: 351.46. Found: 351.1.

Workup

  1. washwashed with brine
  2. extractionThe aqueous layer was back-extracted with ethyl acetate
  3. dry with materialthe combined organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-8ff0aea244f642588fac393337278527
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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