HCID 58109136, compound → HCID 58109725, compound

HRID 2037579Notes

Reaction equation

HRID 2037579 reaction equation
[F:1][CH:2]([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:24][C:25](=[O:27])[CH3:26])([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:14][C:13]2=[O:28])[CH3:11])=[CH:6][CH:5]=1.[CH3:30][Mg]Br>C1COCC1>[F:29][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:24][C:25]([OH:27])([CH3:30])[CH3:26])([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[O:14][C:13]2=[O:28])[CH3:11])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 58109136HCID 58109136, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 58109725HCID 58109725, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(2-oxopropyl)-6-phenyl-1,3-oxazinan-2-one (150 mg, 0.39 mmol) in THF (10 mL) was added methylmagnesium bromide (1 M, 2.5 mL) under nitrogen at −78° C. The mixture was stirred at rt until the reaction was over. The reaction was quenched with satd aq NH4Cl. The organic phase was separated and concentrated to give crude product, which was purified by preparative HPLC to give (S)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (15 mg, 10%). 1H NMR (CDCl3): 1.05 (s, 3H), 1.10 (s, 3H), 1.45 (s, 3H), 2.10 (m, 1H), 2.16 (m, 2H), 2.20 (m, 1H), 2.33 (m, 1H), 2.76 (m, 1H), 5.60 (m, 1H), 6.16-6.58 (m, 1H), 6.78 (m, 2H), 6.86 (m, 2H), 7.26 (m, 5H).

Workup

  1. customThe reaction was quenched with satd aq NH4Cl
  2. customThe organic phase was separated
  3. concentrationconcentrated
  4. customto give crude product, which
  5. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-02e649cb13b84a8c8f5cb5e487207648
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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