Hydrochloric Acid → 1-((6-(4-(Trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)methyl)azetidine-3-carboxylic acid

HRID 2404152Notes

Reaction equation

[F:1][C:2]([F:30])([F:29])[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([CH2:20][N:21]2[CH2:24][CH:23]([C:25]([O:27]C)=[O:26])[CH2:22]2)[CH:14]=[CH:13]3)[CH2:5][CH2:4]1.[OH-].[Na+].Cl>CCO>[F:30][C:2]([F:1])([F:29])[CH:3]1[CH2:4][CH2:5][CH:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([CH2:20][N:21]2[CH2:22][CH:23]([C:25]([OH:27])=[O:26])[CH2:24]2)[CH:14]=[CH:13]3)[CH2:7][CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 1-((6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)methyl)azetidine-3-carboxylate (100 mg, 0.26 mmol) in EtOH (15 mL) was added aqueous NaOH (3 mL, 20%, 5.0 eq.) and refluxed for 1 h. Then the reaction was cooled to 0° C., the pH of the solution was adjusted to 6 using 1M HCl, concentrated and the residue was dissolved in DCM, washed with water, dried and concentrated to give the title compound as a slight yellow solid (50 mg, yield: 52%). ESI-MS (M+1)+: 408.2 HPLC: 94.97%. 1H NMR (400 MHz, CD3OD) δ: 7.77 (d, 1H), 7.69 (d, 1H), 7.64 (s, 1H), 7.33 (d, 1H), 7.31 (s, 1H), 7.16 (dd, 1H), 4.80-4.71 (m, 1H), 3.57 (s, 2H), 3.25 (t, 2H), 3.09 (t, 2H), 2.79-2.73 (m, 1H), 2.41 (br, 1H), 2.07 (d, 2H), 1.80-1.60 (m, 6H).

Workup

temperaturerefluxed for 1 h
concentrationconcentrated
dissolutionthe residue was dissolved in DCM
washwashed with water
customdried
concentrationconcentrated

Sources & evidence

ORD record: ord-492f704a59b24a319f08bb8fc805ed2d
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802659B2

Reaction notes

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