Cyclohexanemethanol → 3-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carbonitrile

HRID 1178695Notes

Reaction equation

HRID 1178695 reaction equation
[OH:1][C:2]1[C:6]([C:7]#[N:8])=[C:5]([S:9][CH3:10])[S:4][N:3]=1.[CH:11]1([CH2:17]O)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CN=2)C=CC=CC=1.CN1CCN(C(N=NC(N2CCN(C)CC2)=O)=O)CC1>C1COCC1.O>[CH:11]1([CH2:17][O:1][C:2]2[C:6]([C:7]#[N:8])=[C:5]([S:9][CH3:10])[S:4][N:3]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 7507CyclohexanemethanolHCID 730434-methyl-N-(4-methylpiperazine-1-carbonyl)iminopiperazine-1-carboxamideHCID 6218932-PyridyldiphenylphosphineHCID 178503646HCID 178503646, compound

Product 1

HCID 695160083-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carbonitrileYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3-hydroxy-5-methylsulfanyl-isothiazole-4-carbonitrile (10 g, 58 mmol) is dissolved in anhydrous THF (200 mL). Cyclohexylmethanol (11 mL, 87.1 mmol) and diphenyl-2-pyridyl-phosphine (30.5 g, 116 mmol) are added to the solution. Diazenedicarboxylic acid bis(N′-methylpiperazide) (32.7 g, 116 mmol) is slurried in anhydrous THF (200 mL) and added dropwise over 1 hour to the reaction. The reaction is stirred at room temp. for 3 days and then diluted with water and extracted with EtOAc (100 mL×3). The combined organics are then dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography (20% EtOAc/hexane) followed by a second chromatography (10% EtOAc/hexane) provides 3 (7.3 g, 52%). 1H NMR (d6 DMSO): δ 4.18 (2H, d, J=6.3 Hz), 2.76 (3H, s), 1.64–1.81 (6H, m), 1.16–1.27 (3H, m), 1.00–1.13 (2H, m).

Workup

  1. additionadded dropwise over 1 hour to the reaction
  2. extractionextracted with EtOAc (100 mL×3)
  3. dry with materialThe combined organics are then dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5f53aeb206fd4ec38e4408bcaa72455a
Source dataset
uspto-grants-2007_10
Patent number
US07276602B2

Reaction notes

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