Sodium Carbonate → (S)-tert-butyl 4-(5-(1-(4-fluorophenyl)vinyl)pyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate

HRID 1498872Notes

Reaction equation

HRID 1498872 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](B2OC(C)(C)C(C)(C)O2)=[CH2:9])=[CH:4][CH:3]=1.Br[C:20]1[CH:21]=[N:22][C:23]([N:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][C@H:27]2[CH2:39][OH:40])=[N:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:20]2[CH:21]=[N:22][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][C@H:27]3[CH2:39][OH:40])=[N:24][CH:25]=2)=[CH2:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 447177702-[1-(4-Fluorophenyl)ethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 118023398(S)-tert-butyl 4-(5-bromopyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate

Product 1

HCID 118023331(S)-tert-butyl 4-(5-(1-(4-fluorophenyl)vinyl)pyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-(1-(4-Fluorophenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (138 mg, 0.556 mmol), (S)-tert-butyl 4-(5-bromopyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (103 mg, 0.276 mmol), 2 M sodium carbonate (0.35 mL, 0.700 mmol), and PdCl2(dppf)-DCM adduct (17.3 mg, 0.021 mmol) were taken up in 1,4-dioxane (2 mL) in a 2-5 mL microwave vial. The reaction was stirred at 100° C. for 18 hours. Room temperature was attained, the reaction mixture was filtered through a plug of Celite eluting with MeOH, and the filtrate was concentrated in vacuo while loading onto Celite. The residue was purified by MPLC (0-100% EtOAc-hexanes) to give (S)-tert-butyl 4-(5-(1-(4-fluorophenyl)vinyl)pyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (107 mg, 0.258 mmol, 94% yield) as an orange gum.

Workup

  1. customRoom temperature
  2. filtrationthe reaction mixture was filtered through a plug of Celite
  3. washeluting with MeOH
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by MPLC (0-100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-cacc7a6752754bbf9e95545eab8b055c
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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