Tetrahydrofuran → HCID 59635693, compound

HRID 1046061Notes

Reaction equation

HRID 1046061 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:39])C.[CH2:40]1[CH2:44][O:43]C[CH2:41]1>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[Br:39][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:44]3([OH:43])[CH2:41][CH2:40]3)[O:13][C:12]2=[O:14])[CH3:16])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 59635808HCID 59635808, compoundHCID 178418443HCID 178418443, 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 M ethylmagnesium 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-9fff0816e90f4543ab38b317e9f3b6e4
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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