Potassium Carbonate → Phenylmethyl (2S)-4-[(5'-cyano-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 2080318Notes

Reaction equation

HRID 2080318 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:12])=[C:7](B(O)O)[CH:8]=1)#[N:2].Br[C:14]1[CH:15]=[C:16]([CH2:20][N:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:28])[C@@H:23]([CH3:37])[CH2:22]2)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:12])=[C:7]([C:18]2[CH:19]=[CH:14][CH:15]=[C:16]([CH2:20][N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[O:28])[C@@H:23]([CH3:37])[CH2:22]3)[CH:17]=2)[CH:8]=1)#[N:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27833615-Cyano-2-fluorobenzeneboronic acidHCID 57730436phenylmethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 57730445Phenylmethyl (2S)-4-[(5'-cyano-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylateYield 92%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To the solution of (5-cyano-2-fluorophenyl)boronic acid (660 mg, 4 mmol) in dioxane/H2O (40 mL/13.3 mL) was added phenylmethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate (1.2 g, 4 mmol), K2CO3 (2.2 g mg, 16 mmol) and Pd(PPh3)4 (230 mg, 0.2 mmol). The resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes then diluted with EtOAc (5 mL). The organic layer was collected and the aqueous layer was extracted with EtOAc (2×5 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by Gilson HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 90/10, v/v, over 12 min), to give the title compound (708 mg, 92%). LC/MS: m/z, 444 (M+H), 1.93 min.

Workup

  1. customThe resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes
  2. customThe organic layer was collected
  3. extractionthe aqueous layer was extracted with EtOAc (2×5 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Gilson HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 90/10

Sources & evidence

ORD record
ord-775e10c02a0a4e7ba6b58bfe94e9c341
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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