Sodium hydride → HCID 67339147, compound

HRID 1045110Notes

Reaction equation

HRID 1045110 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:8])[CH2:6][OH:7].CS([C:13]1[N:17]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:16]2[CH:26]=[CH:27][C:28]([C:30]#[C:31][C:32]3[CH:37]=[CH:36][C:35]([CH2:38][OH:39])=[CH:34][CH:33]=3)=[CH:29][C:15]=2[N:14]=1)(=O)=O>C1COCC1.C(#N)C>[OH:39][CH2:38][C:35]1[CH:36]=[CH:37][C:32]([C:31]#[C:30][C:28]2[CH:27]=[CH:26][C:16]3[N:17]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:13]([O:7][CH2:6][C:5]([OH:4])=[O:8])=[N:14][C:15]=3[CH:29]=2)=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 66774Methyl GlycolateHCID 67340089HCID 67340089, compound2×

Product 1

HCID 67339147HCID 67339147, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 20 mL scintillation vial equipped with a septum cap and a magnetic stirring bar was charged under N2 with NaH (12.0 mg, 60% suspension in mineral oil, 0.30 mmol). A solution of hydroxyacetic acid methyl ester (54.0 mg, 0.60 mmol) in THF (1.0 mL) was added dropwise to the vial. Immediately after the addition was complete, a solution of {4-[2-methanesulfonyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-5-ylethynyl]-phenyl}-methanol (compound 47-1, 49.1 mg, 0.100 mmol) in THF (1 mL) was added. The resulting yellowish suspension was stirred at it for 5 min, then diluted with ACN (2 mL) and quenched by addition of water (2 mL). The resulting solution was stirred at it for 5 min, then an additional 15 min at 65° C. The solution was acidified with 5% aqueous HCl and extracted with EtOAc (three times, 3 mL). The organic layers were combined and washed with 5% aqueous HCl and water and evaporated to dryness in vacuo to give the crude product as yellowish solid. LR-MS (APT-ES): mixture of two N-SEM isomers, calculated for C24H27ClN2O5Si 486.2, observed m/e 487.0 (M+H)+ (Rt 3.09, 3.20 min). The crude product was used in the next step without further purification.

Workup

  1. customA 20 mL scintillation vial equipped with a septum
  2. customcap
  3. additionImmediately after the addition
  4. customquenched by addition of water (2 mL)
  5. stirringThe resulting solution was stirred at it for 5 min
  6. customan additional 15 min
  7. customat 65° C
  8. extractionextracted with EtOAc (three times, 3 mL)
  9. washwashed with 5% aqueous HCl and water
  10. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-490fdbaded76448886e2c3387d9f56cf
Source dataset
uspto-grants-2013_10
Patent number
US08563746B2

Reaction notes

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