Lithium hydroxide, monohydrate → HCID 56646614, compound

HRID 579210Notes

Reaction equation

HRID 579210 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[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][O:13][C@H:12]([CH2:22][CH:23]([OH:25])[CH3:24])[C:11]1=[O:26])=[O:4].O[Li].O>C1COCC1.CO.O>[CH:16]1([C@H:15]2[N:10]([C:9]3[CH:8]=[C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])[S:6][C:5]=3[C:3]([OH:4])=[O:2])[C:11](=[O:26])[C@@H:12]([CH2:22][C@@H:23]([OH:25])[CH3:24])[O:13][CH2:14]2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66683725HCID 66683725, compound

Product 1

HCID 56646614HCID 56646614, compoundYield 16.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[(2R,5R)-5-cyclohexyl-2-(2-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (420 mg, 0.91 mmol, 1.0 equiv) in THF (8 mL), MeOH (4 mL) and water (4 mL) was added LiOH.H2O (115 mg, 2.73 mmol, 3.0 equiv). The resulting solution was stirred at room temperature for one hour. The volatile solvent was removed under vacuum and the residue was acidified by addition of 3.0 N HCl aqueous solution until pH=1. The mixture was extracted with EtOAc (50 mL). The separated organic layer was washed with brine (10 mL), dried (over Na2SO4) and concentrated. The residue was purified by HPLC (0.1% NH4OH) to give product (68 mg, 16.7%). MS: 448.2 [M−H+]. 1H NMR (400 MHz, CD3OD) δ 1.07-1.31 (m, 8H) 1.32 (s, 9H) 1.45-1.60 (m, 2H) 1.63-1.85 (m, 4H) 1.87-1.98 (m, 1H) 2.02-2.11 (m, 1H) 3.60-3.66 (m, 1H) 3.93-4.03 (m, 2H) 4.15 (d, 1H) 4.26-4.35 (m, 1H) 6.94 (s, 1H).

Workup

  1. customThe volatile solvent was removed under vacuum
  2. additionthe residue was acidified by addition of 3.0 N HCl aqueous solution until pH=1
  3. extractionThe mixture was extracted with EtOAc (50 mL)
  4. washThe separated organic layer was washed with brine (10 mL)
  5. dry with materialdried (over Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by HPLC (0.1% NH4OH)

Sources & evidence

ORD record
ord-6f394602362a4fc28d65cd9a2c928fae
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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