HCID 58109155, compound → HCID 58109324, compound

HRID 2037614Notes

Reaction equation

HRID 2037614 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:24][CH:25]=[O:26])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:27][Mg+].[Br-]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:24][CH:25]([OH:26])[CH3:27])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 58109155HCID 58109155, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 58109324HCID 58109324, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-((S)-6-(4-fluorophenyl)-3-((S)-1-(4-fluorophenyl)ethyl)-2-oxo-1,3-oxazinan-6-yl)acetaldehyde (500 mg, 1.40 mmol) in anhydrous THF (100 mL) was added CH3MgBr (5 mL, 3 mol/L) at −78° C. under nitrogen. The formed mixture was stirred for 3 h at −78° C. The reaction was quenched by water. The organic phase was separated and concentrated to give the crude product, which was purified by TLC and chiral preparative HPLC to afford (6S)-6-(4-fluorophenyl)-3-((S)-1-(4-fluorophenyl)ethyl)-6-(2-hydroxypropyl)-1,3-oxazinan-2-one (19 mg, 4%). LC-MS Method 2 tR=1.92 min, m/z=398; 1H NMR: (400 MHz, CDCl3): δ=1.02 (d, 3H), 1.48 (d, 3H), 1.84 (m, 4H), 2.01 (m, 1H), 2.14 (m, 1H), 2.29 (m, 1H), 2.84 (m, 1H), 3.83 (m, 1H), 5.54 (q, 1H), 6.74 (m, 2H), 6.82 (m, 2H), 6.99 (m, 2H), 7.21 (m, 1H).

Workup

  1. customThe reaction was quenched by water
  2. customThe organic phase was separated
  3. concentrationconcentrated
  4. customto give the crude product, which
  5. customwas purified by TLC and chiral preparative HPLC

Sources & evidence

ORD record
ord-131dbf478cd344b396c55cf0f5d20803
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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