Hydrochloric Acid → 5-((4-(tert-Butoxycarbonyl)morpholin-2-yl)methoxy)-2'-cyano-4'-methylbiphenyl-3-carboxylic acid

HRID 1845324Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:15]=[C:14]([C:16]([O:18]C)=[O:17])[CH:13]=[C:12]([O:20][CH2:21][CH:22]2[O:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]2)[CH:11]=1)#[N:2].[OH-].[Li+].Cl>C1COCC1>[C:31]([O:30][C:28]([N:24]1[CH2:25][CH2:26][O:27][CH:22]([CH2:21][O:20][C:12]2[CH:13]=[C:14]([C:16]([OH:18])=[O:17])[CH:15]=[C:10]([C:4]3[CH:5]=[CH:6][C:7]([CH3:9])=[CH:8][C:3]=3[C:1]#[N:2])[CH:11]=2)[CH2:23]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of tert-butyl 2-((2′-cyano-5-(methoxycarbonyl)-4′-methylbiphenyl-3-yloxy)methyl)morpholine-4-carboxylate (107 mg, 0.23 mmol) in THF (2 mL) was added 2.5 M of aq. lithium hydroxide solution (0.52 mL, 1.3 mmol). The reaction mixture was stirred at 60° C. overnight, and then acidified with 15% HCl (aq.) to pH=5, and extracted with EtOAc. The combined organic layers were concentrated in vacuo to get the title compound. 1H NMR (CDCl3, 400 MHz): 7.86 (t, 1H, J=1.6 Hz), 7.70 (t, 1H, J=1.6 Hz), 7.59 (s, 1H), 7.47 (dd, 1H, J=8.0, 1.2 Hz), 7.42 (d, 1H, J=8.0 Hz), 7.37 (s, 1H), 4.20-3.56 (m, 7H), 3.10-2.90 (m, 2H), 2.45 (s, 3H), 1.49 (s, 9H).

Workup

extractionextracted with EtOAc
concentrationThe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record: ord-2cdf894f468e4aaea6d0808c8d39eeef
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946439B2

Reaction notes

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