HCID 58109492, compound → HCID 58109208, compound

HRID 2037550Notes

Reaction equation

HRID 2037550 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:24][CH2:25][CH2:26][OH:27])([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)(=[O:3])[CH3:2].[CH3:29][Mg]Br>C1COCC1>[OH:3][C:1]([C:4]1[CH:5]=[CH:6][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:24][CH2:25][CH2:26][OH:27])([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:14][C:13]2=[O:28])[CH3:11])=[CH:8][CH:9]=1)([CH3:29])[CH3:2]

Participants

4

Reactant 2

HCID 58109492HCID 58109492, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 58109208HCID 58109208, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-3-((S)-1-(4-acetylphenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one (40 mg, 0.1 mmol) in THF (10 mL) was added dropwise methylmagnesium bromide (3 M, 1 mL, 1 mmol) at −78° C. under N2. The mixture was stirred at rt for 2 days. The reaction was quenched with water, and the layers were separated. The aqueous layer was extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product, which was purified by preparative HPLC to give (R)-3-((S)-1-(4-(2-hydroxypropan-2-yl)phenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one (5 mg, 13%). 1H NMR (CDCl3): 1.31 (m, 1H), 1.44 (m, 3H), 1.64 (m, 1H), 1.93 (m, 2H), 2.11-2.25 (m, 3H), 2.82 (m, 1H), 3.51 (m, 2H), 5.58 (m, 1H), 6.81 (m, 2H), 7.14 (m, 2H), 7.27 (m, 5H). LC-MS Method 2 tR=1.141, min, m/z=420.

Workup

  1. customThe reaction was quenched with water
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-a4ba3006729d4410928c85d8bbc4e785
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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