Hydrochloric Acid → HCID 66692147, compound

HRID 579185Notes

Reaction equation

HRID 579185 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][CH2:13][C@H:12]([OH:22])[C:11]1=[O:23])=[O:4].O[Li].O.Cl.[CH2:34]1COCC1.O.CO>>[CH3:28][C:26]([CH3:29])([CH3:27])[C:25]#[C:24][C:7]1[S:6][C:5]([C:3]([OH:2])=[O:4])=[C:9]([N:10]2[C@H:15]([CH:16]([CH2:21][CH3:20])[CH2:17][CH2:18][CH2:19][CH3:34])[CH2:14][CH2:13][C@H:12]([OH:22])[C:11]2=[O:23])[CH:8]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 21892291Methanol tetrahydrofuran waterHCID 66684775HCID 66684775, compound

Product 1

HCID 66692147HCID 66692147, compoundYield 57%

Conditions

Temperature
50 °C

Procedure

To a solution of 3-((3S,6S)-6-Cyclohexyl-3-hydroxy-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (1.5 g, 3.59 mmol, 1 equiv.) in THF/H2O/MeOH (5.0 mL/5.0 mL/1.0 mL) was added LiOH.H2O (0.79 g, 17.56 mmol, 5.0 equiv.) at room temperature. The reaction mixture was stirred at 50° C. for 20 minutes. The reaction was then acidified to pH=5 by addition of 3.0 N HCl aq. solution and the mixture 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 850 mg of product (yield 57%). MS: 404 [M+H+]. 1H-NMR (400 MHz, MeOD): δ 6.95 (s, 1H), 4.09 (m, 1H), 3.74 (m, 1H), 2.09 (m, 1H), 1.94-1.67 (m, 8H), 1.38 (m, 1H), 1.33 (s, 9H), 1.17 (m, 5H).

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. 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-bb5ab0c2f33c42238781db21826679b9
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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