Hydrogen Peroxide → HCID 59627239, compound

HRID 1523249Notes

Reaction equation

HRID 1523249 reaction equation
[CH2:1]([C@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:26])[NH:5]1)[CH:2]=[CH2:3].[OH-:34].[Na+].OO>C1COCC1>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[C:15]1[CH:14]=[CH:13][C:12]([C@@H:10]([N:7]2[CH2:8][CH2:9][C@@:4]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH2:1][CH2:2][CH2:3][OH:34])[NH:5][C:6]2=[O:26])[CH3:11])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 59627218HCID 59627218, compound

Product 1

HCID 59627239HCID 59627239, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (R)-4-allyl-1-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-4-(4-fluorophenyl)tetrahydropyrimidin-2(1H)-one (42 mg, 0.092 mmol) in THF (10 mL) was added 1M BH3 in THF (1.5 mL, 1.5 mmol) at 0° C. under nitrogen. The mixture was stirred for 2 h. The reaction was quenched by water. 3 M aq NaOH (0.3 mL, 3 mmol) and H2O2 (3 mL) were added. The resulting mixture was stirred for 1.5 h. The mixture was extracted with EtOAc and the combined organic phase was concentrated to give the crude product, which was purified by preparative HPLC to give (R)-1-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-4-(4-fluorophenyl)-4-(3-hydroxypropyl)tetrahydropyrimidin-2(1H)-one (8 mg, 19%). LC-MS Method 1 tR=1.413 min, m/z=469.2; 1H NMR (CDCl3): δ=1.36 (m, 2H), 1.45 (m, 3H), 1.91-2.01 (m, 5H), 2.18 (m, 1H), 2.83 (m, 1H), 3.52 (m, 2H), 5.76 (m, 2H), 6.09 (m, 1H), 6.38-6.98 (m, 4H), 7.16 (m, 2H), 7.22 (m, 1H), 7.25 (m, 1H), 7.28 (m, 3H).

Workup

  1. customat 0° C.
  2. customThe reaction was quenched by water
  3. stirringThe resulting mixture was stirred for 1.5 h
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationthe combined organic phase was concentrated
  6. customto give the crude product, which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-c03c8a2310fc409fa23f026a61bdd86d
Source dataset
uspto-grants-2015_07
Patent number
US09079861B2

Reaction notes

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