Tetrahydrofuran → HCID 59635693, compound

HRID 406625Notes

Reaction equation

HRID 406625 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:31]C(OC)=O)[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](C4C=CC(=O)N(C)C=4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C[Mg][Br:38].[CH2:39]1[CH2:43][O:42]C[CH2:40]1>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[Br:38][C:20]1[CH:21]=[CH:22][C:17]([C@@H:15]([N:11]2[CH2:10][CH2:9][C@@:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)([CH2:31][C:43]3([OH:42])[CH2:40][CH2:39]3)[O:13][C:12]2=[O:14])[CH3:16])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 59635808HCID 59635808, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59635693HCID 59635693, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 178460666HCID 178460666, compoundCatalyst

Procedure

To a solution of methyl 2-((S)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-ethyl)-2-oxo-1,3-oxazinan-6-yl)acetate (150 mg, 0.33 mmol), and tetraisopropoxytitanium (189 mg, 0.66 mmol) in THF (20 mL) was added 3.0 Methylmagnesium bromide (4 mL, 12 mmol) at rt under nitrogen. Then the mixture was stirred for 2 h. The reaction was quenched with aqueous NH4Cl solution, and the mixture was filtered. The filtrate was extracted with EtOAc. The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated to give the crude product, which was purified by preparative HPLC to give (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-((1-hydroxycyclopropyl)methyl)-1,3-oxazinan-2-one (2.51 mg, 2%). 1H NMR (CDCl3): 0.03 (m, 1H), 0.18 (m, 1H), 0.49 (m, 1H), 0.60 (m, 1H), 1.43 (m, 3H), 2.08 (s, 2H), 2.26 (m, 1H), 2.37 (m, 2H), 2.88 (m, 1H), 5.53 (m, 1H), 6.66 (d, 2H), 6.97 (t, 2H), 7.16 (m, 2H), 7.26 (m, 2H).

Workup

  1. customThe reaction was quenched with aqueous NH4Cl solution
  2. filtrationthe mixture was filtered
  3. extractionThe filtrate was extracted with EtOAc
  4. washThe combined organic phase was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-945f28735f81458ab84af6233bb9c21f
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Reaction notes

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