Lithium Hexamethyldisilazide → 4-[5-(2-Ethoxy-vinyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

HRID 1690732Notes

Reaction equation

HRID 1690732 reaction equation
[Cl-].[CH2:2]([O:4][CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH3:3].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:35][C:36]1([CH3:54])[CH:45]([N:46]2[C:50]([CH:51]=O)=[CH:49][N:48]=[CH:47]2)[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38](=[O:53])[O:37]1>C1COCC1>[CH2:2]([O:4][CH:5]=[CH:51][C:50]1[N:46]([CH:45]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:38](=[O:53])[O:37][C:36]2([CH3:54])[CH3:35])[CH:47]=[N:48][CH:49]=1)[CH3:3]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 21470303(Ethoxymethyl)(triphenyl)phosphanium chlorideHCID 248026903-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbaldehyde

Product 1

HCID 669067104-[5-(2-Ethoxy-vinyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethoxymethyltriphenylphosphonium chloride (0.426 g, 1.2 mmol) in THF (5 mL) at ambient temperature is added lithium hexamethyldisilazide (1M in THF, 1.3 mL, 1.3 mmol) and the mixture is stirred for 15 min. 3-(3,3-Dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbaldehyde (0.27 g, 1.0 mmol) (Example 9a) in THF (5 mL) and the mixture is stirred at ambient temperature overnight, then filtered. The filtrate is concentrated in vacuo to give crude 4-[5-(2-ethoxy-vinyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one, which is redissolved in methanol (5 mL). Pd/C (0.500 g) is added and the reaction vessel is flushed with hydrogen gas and stirred under balloon pressure at 50° C. overnight. The mixture is filtered, and the filtrate is concentrated in vacuo to give a residue which is purified by semi-preparative reverse phase HPLC to give 4-[5-(2-ethoxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one as a white solid; MS (ESI) m/z 315.0 (M+H); 1H NMR (400 MHz, MeOD) of the HCl salt δ ppm 1.25 (t, J=6.9 Hz, 3 H), 1.32 (s, 3 H), 1.62 (s, 3 H), 3.29-3.37 (m, 2 H), 3.60-3.69 (m, 2 H), 3.79-3.97 (m, 2 H), 6.09 (s, 1 H), 7.57 (s, 1 H), 7.64 (d, J=7.6 Hz, 1 H), 7.73-7.79 (m, 1 H), 7.81-7.88 (m, 1 H), 8.32 (dd, J=7.7, 1.4 Hz, 1 H), 8.63 (br. s, 1H)

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-4ef7595c947a44ac95ede5d5839dd4c2
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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