Sodium hydride → HCID 58303817, compound

HRID 1886985Notes

Reaction equation

HRID 1886985 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[S:15][C@@H:16]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C@@H:17]([OH:21])[C:18](=[O:20])[NH:19][C:13]=2[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl.[CH3:33][N:34]([CH3:38])[CH2:35][CH2:36]Cl.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[C:14]2[S:15][C@@H:16]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[C@@H:17]([OH:21])[C:18](=[O:20])[N:19]([CH2:36][CH2:35][N:34]([CH3:38])[CH3:33])[C:13]=2[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 86654321HCID 86654321, compound

Product 1

HCID 58303817HCID 58303817, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
22 °C

Procedure

To a solution of 751 mg (1.85 mmol) of (+/−)-(2S,3S)-9-(benzyloxy)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one in 7 mL of DMF was added 81 mg (2.03 mmol) of sodium hydride (60% dispersion in mineral oil). The mixture was stirred at 22° C. for 30 minutes. In a separate flask, 408 mg (2.03 mmol) of 2-(dimethylamino)ethylchloride hydrochloride and 81 mg (2,03 mmol) of sodium hydride (60% dispersion in mineral oil), was added to 7 mL of DMF. The mixture was stirred for 30 minutes at 22° C. and then added to the former mixture. The reaction was heated to 45° C. and stirred for 27 hours. A mixture of 1:1 saturated NaHCO3 and water was added to the reaction, and the mixture was extracted with ethyl acetate (3×). The organic layers were combined, washed with brine, dried (Na2SO4), and evaporated. The resulting crude product was purified by flash chromatography on silica gel, eluting first with DCM then gradually increasing to 3.5% methanol/DCM to give (+/−)-(2S,3S)-9-(benzyloxy)-5-(2-(dimethylamino)ethyl)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one.

Workup

  1. stirringThe mixture was stirred for 30 minutes at 22° C.
  2. additionadded to the former mixture
  3. temperatureThe reaction was heated to 45° C.
  4. stirringstirred for 27 hours
  5. additionwas added to the reaction
  6. extractionthe mixture was extracted with ethyl acetate (3×)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customThe resulting crude product was purified by flash chromatography on silica gel
  11. washeluting first with DCM
  12. temperaturethen gradually increasing to 3.5% methanol/DCM

Sources & evidence

ORD record
ord-246b1958975b4a24b3a197f72ccc3648
Source dataset
uspto-grants-2013_08
Patent number
US08501727B2

Reaction notes

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