Sodium hydride → HCID 58387150, compound

HRID 1045113Notes

Reaction equation

HRID 1045113 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:11])[C:6]([CH3:10])([CH3:9])[CH2:7][OH:8].[Cl:12][C:13]1[C:14]([C:34]#[C:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:15][C:16]2[N:20]=[C:19](S(C)(=O)=O)[N:18]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:17]=2[CH:33]=1>C1COCC1>[Cl:12][C:13]1[C:14]([C:34]#[C:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[CH:15][C:16]2[N:20]=[C:19]([O:8][CH2:7][C:6]([CH3:10])([CH3:9])[C:5]([OH:4])=[O:11])[N:18]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:31])([CH3:32])[CH3:30])[C:17]=2[CH:33]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 84152Methyl 3-hydroxypivalateHCID 58387189HCID 58387189, compound

Product 1

HCID 58387150HCID 58387150, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 20 mL scintillation vial equipped with a septum cap and a magnetic stirring bar was charged under N2 with NaH (18.0 mg, 60% suspension in mineral oil, 0.45 mmol). In a separate vial, a solution of 3-hydroxy-2,2-dimethyl-propionic acid methyl ester (79.0 mg, 0.600 mmol) in THF (2.0 mL) was combined with a solution of compound 49-2 (138.0 mg, 0.300 mmol), and added dropwise to the 20 mL scintillation vial containing NaH. The resulting mixture was stirred at rt for 5 min, then cooled in a ice bath (0° C.) and quenched by a dropwise addition of water (6 mL). The mixture was allowed to warm up to rt and stirring was maintained for 5 min. The mixture was acidified with 5% aqueous HCl and extracted with EtOAc (three times, 3 mL). The organic layers were combined and evaporated to dryness in vacuo. The residue was dissolved in ACN (4 mL) and added to a vial containing 5% aqueous LiOH (1 mL). The resulting mixture was stirred at 65° C. for 1 h, then acidified with 5% aqueous HCl and extracted with EtOAc (three times, 3 mL). The organic layers were combined and evaporated to dryness in vacuo. The crude product was used in the next step without further purification. LR-MS (API-ES): mixture of two N-SEM isomers, calculated for C26H31ClN2O4Si 498.2, observed m/e 499.0 (M+H)+ (Rt 3.78. 3.87 min).

Workup

  1. customA 20 mL scintillation vial equipped with a septum
  2. customcap
  3. additionadded dropwise to the 20 mL scintillation vial
  4. temperaturecooled in a ice bath (0° C.)
  5. customquenched by a dropwise addition of water (6 mL)
  6. temperatureto warm up to rt
  7. stirringstirring
  8. temperaturewas maintained for 5 min
  9. extractionextracted with EtOAc (three times, 3 mL)
  10. customevaporated to dryness in vacuo
  11. dissolutionThe residue was dissolved in ACN (4 mL)
  12. additionadded to
  13. additiona vial containing 5% aqueous LiOH (1 mL)
  14. stirringThe resulting mixture was stirred at 65° C. for 1 h
  15. extractionextracted with EtOAc (three times, 3 mL)
  16. customevaporated to dryness in vacuo
  17. customThe crude product was used in the next step without further purification
  18. additionLR-MS (API-ES): mixture of two N-SEM isomers
  19. customm/e 499.0 (M+H)+ (Rt 3.78. 3.87 min)

Sources & evidence

ORD record
ord-6516203d18e048f897323c8e9f5ead2f
Source dataset
uspto-grants-2013_10
Patent number
US08563746B2

Reaction notes

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