Cesium carbonate → 2-Amino-6-cyclopropylbenzonitrile

HRID 471777Notes

Reaction equation

HRID 471777 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6](Br)[C:3]=1[C:4]#[N:5].C[C:12]1(C)[CH2:14][CH:13]1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.C1(P([Pd-4](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)C=CC=CC=1>[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:12]2[CH2:14][CH2:13]2)[C:3]=1[C:4]#[N:5]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 98130382-Amino-6-bromobenzonitrileHCID 57416253(2,2-Dimethylcyclopropyl)boronic acid

Product 1

HCID 667472522-Amino-6-cyclopropylbenzonitrileYield 40,578.602%

Reagents, catalysts & solvents 3

HCID 178420553HCID 178420553, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a degassed solution of 2-amino-6-bromobenzonitrile (851 μmol, 168 mg), 2,2-dimethylcyclopropylboronic acid (1.106 μmol, 126 mg) (Example 270b), and Cs2CO3 (2.979 mmol, 970 mg) in DME (3.4 mL) and water (850 μL) was added tetrakis(triphenylphosphino)palladium(0) (43 μmol, 50 mg) under nitrogen and the reaction mixture microwaved for 2 hours at 160° C. The reaction mixture was cooled to room temperature and extracted with EtOAc (3×5 mL). The combined organic layers was washed once with brine (5 mL), dried over sodium sulfate, filtered and evaporated. The crude product was purified on silica gel (EtOAc/hexanes 10%-40%) to give the desired product (71 mg, 45%) as a waxy, yellow solid. 1H NMR (400 MHz, CDCl3) δ 0.82 (m, 1H), 0.82 (s, 3H), 0.85 (m, 1H), 1.33 (s, 3H), 1.92 (m, 1H), 4.36 (br. s, 2H), 6.47 (d, J=8 Hz, 1H), 6.56 (d, J=8 Hz, 1H), 7.20 (t, J=8 Hz, 1H).

Workup

  1. customthe reaction mixture microwaved for 2 hours at 160° C
  2. extractionextracted with EtOAc (3×5 mL)
  3. washThe combined organic layers was washed once with brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified on silica gel (EtOAc/hexanes 10%-40%)

Sources & evidence

ORD record
ord-c0397a059b544b63abb044a6698163eb
Source dataset
uspto-grants-2014_01
Patent number
US08633186B2

Reaction notes

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