Sodium Hydroxide → 3-((1-(Tert-butoxycarbonyl)piperidin-4-yl)oxy)-5-chloro-2-methylbenzoic acid

HRID 1050464Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:23]([O:25]C)=[O:24])[C:5]([CH3:22])=[C:6]([CH:21]=1)[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[OH-].[Na+]>CO>[C:17]([O:16][C:14]([N:11]1[CH2:10][CH2:9][CH:8]([O:7][C:6]2[C:5]([CH3:22])=[C:4]([CH:3]=[C:2]([Cl:1])[CH:21]=2)[C:23]([OH:25])=[O:24])[CH2:13][CH2:12]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of tert-butyl 4-(5-chloro-3-(methoxycarbonyl)-2-methylphenoxy)piperidine-1-carboxylate (250 mg, 0.651 mmol) in methanol (1.0 mL) was added 6 N NaOH (2.1 mL, 13.03 mmol). The reaction was heated at 55° C. for 18 h. The reaction was cooled to RT and concentrated in vacuo. The residue was then suspended in water and acidified with 1N HCl solution, filtered, and dried to give 3-((1-(tert -butoxycarbonyl)piperidin-4-yl)oxy)-5-chloro-2-methylbenzoic acid (0.180 g, 0.487 mmol, 75% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.41 (s, 9 H) 1.56 (m, J=12.47, 8.31, 4.14, 4.14 Hz, 2 H) 1.76-1.97 (m, 2 H) 2.23-2.35 (m, 3 H) 3.19-3.31 (m, 2 H) 3.48-3.63 (m, 2 H) 4.70 (dt, J=7.26, 3.82 Hz, 1 H) 7.31 (dd, J=11.37, 2.02 Hz, 2 H) 13.22 (br. s., 1 H). MS(ES) [M+H]+ 370.2.

Workup

temperatureThe reaction was cooled to RT
concentrationconcentrated in vacuo
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-6de44cdb74264d6a9cbb5e1778d79bed
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382234B2

Reaction notes

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