Lithium hydroxide, monohydrate → 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acid

HRID 333896Notes

Reaction equation

HRID 333896 reaction equation
[OH:1][C:2]([CH3:38])([CH3:37])[CH2:3][C@@:4]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([CH3:30])([CH3:29])[C:22]([O:24]CCCC)=[O:23])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.O[Li].O>C1COCC1.O.CO>[OH:1][C:2]([CH3:37])([CH3:38])[CH2:3][C@@:4]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([CH3:30])([CH3:29])[C:22]([OH:24])=[O:23])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66869601butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate

Product 1

HCID 498703204-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acidYield 72%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a stirred solution of butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate (11.3 mg, 0.022 mmol) in 1:1:2 THF/H2O/MeOH (2 mL) was added LiOH.H2O (60 mg, 1.4 mmol). The mixture was stirred at rt for 1 day and concentrated. The residue was purified by prep HPLC to afford 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acid (7 mg, 72%) as a solid. LC-MS Method 1 tR=1.58 min, m/z=464, 406; 1H NMR (CDCl3) 1.12 (s, 3H), 1.18 (s, 3H), 1.51 (d, 3H), 1.58 (s, 6H), 2.10-2.40 (5H), 2.90 (m, 1H), 5.67 (q, 1H), 6.86 (d, 2H), 7.18 (d, 2H), 7.30-7.40 (5H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-3d34ed40f50747c687561f5e4796a4a1
Source dataset
uspto-grants-2014_11
Patent number
US08883778B2

Reaction notes

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