Tetrahydrofuran → [2-Fluoro-4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-carbamic acid tert-butyl ester

HRID 1392232Notes

Reaction equation

HRID 1392232 reaction equation
[CH2:1]([N:5]1[CH:9]=[CH:8][N:7]=[N:6]1)[CH2:2][CH:3]=[CH2:4].C1COCC1.[C:15]([O:19][C:20](=[O:30])[NH:21][C:22]1[CH:27]=[CH:26][C:25](Br)=[CH:24][C:23]=1[F:29])([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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].O>[C:15]([O:19][C:20](=[O:30])[NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:4][CH2:3][CH2:2][CH2:1][N:5]2[CH:9]=[CH:8][N:7]=[N:6]2)=[CH:24][C:23]=1[F:29])([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 190682081-but-3-enyl-1H-[1,2,3]triazoleHCID 22736228tert-butyl N-(4-bromo-2-fluorophenyl)carbamate

Product 1

HCID 69220904[2-Fluoro-4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-but-3-enyl-1H-[1,2,3]triazole (0.85 g, 6.9 mmol) in THF (15 ml) 9-borabicyclo[3.3.1]nonane (0.5 M in THF, 30.3 ml, 15.2 mmol) was added dropwise at 0° C. and stirring continued for 2 h. This mixture was then added to a solution of (4-bromo-2-fluoro-phenyl)-carbamic acid tert-butyl ester (2 g, 6.89 mmol), Pd(dppf)Cl2 (0.56 g, 0.69 mmol) and aqueous cesium carbonate (6.89 ml, 3M) in DMF (30 ml) and stirred for 3 h at 70° C. Water (100 ml) was added and the mixture extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified on silica gel (ethyl acetate) to yield [2-Fluoro-4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-carbamic acid tert-butyl ester as light yellow solid. Yield 1.93 g (84%)

Workup

  1. stirringstirred for 3 h at 70° C
  2. extractionthe mixture extracted with ethyl acetate (3×100 ml)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-01ef786061ec438693154980bc49804b
Source dataset
uspto-grants-2008_03
Patent number
US07342030B2

Reaction notes

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