Allyl bromide → HCID 58109363, compound

HRID 2037535Notes

Reaction equation

HRID 2037535 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@@:20]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)([CH2:23][CH2:24][OH:25])[O:19][C:18]2=[O:33])[CH3:16])=[CH:11][CH:10]=1.[H-].[Na+].[CH2:36](Br)[CH:37]=[CH2:38]>C1COCC1>[CH2:38]([O:25][CH2:24][CH2:23][C@@:20]1([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[O:19][C:18](=[O:33])[N:17]([C@H:15]([C:12]2[CH:13]=[CH:14][C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:10][CH:11]=2)[CH3:16])[CH2:22][CH2:21]1)[CH:37]=[CH2:36]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 53361128HCID 53361128, compound

Product 1

HCID 58109363HCID 58109363, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydro-xyethyl)-1,3-oxazinan-2-one (100 mg, 0.22 mmol) in THF (5 mL) was added NaH (30 mg, 1.10 mmol) at 0° C. After stirring for 1 h, allyl bromide (79 mg, 0.66 mmol) was added, and the mixture was stirred at rt overnight. The reaction was quenched with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative TLC to give (S)-6-(2-(allyloxy)ethyl)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (100 mg, 92%) 1H NMR (CDCl3): 1.47-1.59 (d, 3H), 2.05-2.15 (m, 2H), 2.21-2.38 (m, 3H), 2.88-2.93 (m, 1H), 3.12-3.19 (m, 1H), 3.52-3.59 (m, 1H). 3.62-3.85 (m, 2H), 5.03-5.18 (m, 2H), 5.61-5.69 (m, 1H), 5.71-5.81 (m, 1H), 6.81-6.92 (m, 3H), 6.92-7.01 (m, 2H), 7.13-7.20 (m, 4H), 7.21-7.26 (m, 3H).

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-c7548eb643fb4f2198d149cd6020f58c
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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