Bromoacetonitrile → HCID 86585176, compound

HRID 1370993Notes

Reaction equation

HRID 1370993 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[NH:16][C:15]2=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:35][C:36]#[N:37]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]([CH2:35][C:36]#[N:37])[C:15]2=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 3251421Potassium bis(trimethylsilyl)amideHCID 13046891tert-Butyl 4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 86585176HCID 86585176, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (2.91 g, 9.16 mmol) in THF (10 mL) was added dropwise to a solution of KHMDS (2.19 g, 11.0 mmol) in THF (20 mL). The mixture was stirred for 10 min then bromoacetonitrile (3.2 mL, 46 mmol) was added. The resulting mixture was stirred for 4 h then partitioned between EtOAc (750 mL) and saturated aqueous NaHCO3 (200 mL). The EtOAc layer was washed with H2O (3×200 mL) and brine (200 mL). The combined washes were extracted with EtOAc (2×150 mL). The combined extracts were dried over Na2SO4 and concentrated. Column chromatography (silica, 20-60% EtOAc/hexanes) afforded 2.20 g (67%) of 4-(3-cyanomethyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester. The purified material was dissolved in CH2Cl2 (40 mL) and diluted with TFA (25 mL). The resulting mixture was stirred for 1 h then diluted with CH2Cl2 (250 mL) and washed with 1 N NaOH (100 mL). The aqueous layer was extracted with CH2Cl2 (2×100 mL). The combined extracts were dried over Na2SO4 and concentrated to 1.59 g (95%) of the title compound which was suitable for further use without purification. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.1. MS (electrospray): m/z calculated for C14H17N4O [M++H] 257.14, found 257.1. 1H NMR (CDCl3, 400 Hz): 733-7.29 (m, 1H), 7.17-7.02 (m, 3H), 4.75 (s, 2H), 4.41 (ft, J=12.2, 4.4 Hz, 1H), 3.28 (brd, J=9.8 Hz, 2H), 3.11 (brs, 1H), 2.80 (t, J=10.0 Hz, 2H), 2.37 (dq, J=12.5, 4.2 Hz, 2H), 1.83 (br d, J=11.8 Hz, 2H).

Workup

  1. stirringThe resulting mixture was stirred for 4 h
  2. customthen partitioned between EtOAc (750 mL) and saturated aqueous NaHCO3 (200 mL)
  3. washThe EtOAc layer was washed with H2O (3×200 mL) and brine (200 mL)
  4. extractionThe combined washes were extracted with EtOAc (2×150 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f5d4a8de4f9749279ffbd1d6947dd95d
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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