Hydrochloric Acid → HCID 66684905, compound

HRID 579206Notes

Reaction equation

C[O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[CH:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][CH2:13][C@@H:12]([CH2:22][CH2:23][OH:24])[C:11]1=[O:25])=[O:4].O[Li].O.Cl>C1COCC1.O.CO>[CH:16]1([CH:15]2[N:10]([C:9]3[CH:8]=[C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])[S:6][C:5]=3[C:3]([OH:4])=[O:2])[C:11](=[O:25])[C@H:12]([CH2:22][CH2:23][OH:24])[CH2:13][CH2:14]2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-[(S)-6-cyclohexyl-3-(2-hydroxy-ethyl)-2-oxo-piperidin-1-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (123 mg, 0.28 mmol, 1 equiv.) in THF/H2O/MeOH (1.0 mL/1.0 mL/0.5 mL) was added LiOH.H2O (60 mg, 1.38 mmol, 5 equiv) and the resulting solution was stirred at 50° C. for 20 minutes. The solution was then acidified to pH=5 by addition of 3.0 N HCl aq. solution. The solution was extracted with EtOAc. The organic layer was dried over Na2SO4, and concentrated. The residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min) to give product 28 mg (yield 23%). MS: 432 [M+H+]. 1H-NMR (400 MHZ, CD3OD): 6.85 (s, 1H), 3.92 (br, 1H), 3.67 (m, 2H), 2.41 (br, 1H), 2.15 (m, 1H), 1.97 (m, 2H), 1.78 (m, 7H), 1.37 (m, 2H), 1.31 (s, 9H), 1.14 (m, 5H).

Workup

extractionThe solution was extracted with EtOAc
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated
customThe residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min)

Sources & evidence

ORD record: ord-10b507ff476747dd8738fc4fe2d8f05f
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040690B2

Reaction notes

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