4-Methylmorpholine → HCID 86757295, compound

HRID 651786Notes

Reaction equation

HRID 651786 reaction equation
C[Si](C)(C)CCO[C:6]([C:8]1([N:14]=[C:15]=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:25][NH:26][C:27]([C@H:29]([C@@H:39]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:40]([NH:42][NH2:43])=[O:41])[CH2:30]/[CH:31]=[CH:32]/[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:28].CN1CCOCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C.CN(C)C=O.ClCCl>[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:25][NH:26][C:27]([C@H:29]([C@@H:39]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:40]([NH:42][N:43]1[C:6](=[O:7])[C:8]2([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[NH:14][C:15]1=[O:16])=[O:41])[CH2:30]/[CH:31]=[CH:32]/[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:28]

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 2724141Tetrabutylammonium FluorideHCID 23252710HCID 23252710, compoundHCID 86757296HCID 86757296, compound

Product 1

HCID 86757295HCID 86757295, compoundYield 45.1%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.269 g of 2-(trimethylsilyl)ethyl-1-isocyanato-1-cyclohexane carboxylate and 0.403 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-4-methylvalerohydrazide in 6 ml of a 5:1 mixture of dichloromethane and dimethylformamide was treated with 0.15 ml of N-methylmorpholine and was stirred for 2 hours at room temperature. The solution was then washed with 5% citric acid solution and then saturated sodium chloride solution, dried over anhydrous magnesium sulphate and evaporated. The residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (2:1) followed by hexane/ethyl acetate (1:1) for the elution. The product obtained was dissolved in 5 ml of tetrahydrofuran and 1.6 ml of a 1.0M solution of tetrabutylammonium fluoride in tetrahydrofuran added. The mixture was stirred for 1.5 hours at room temperature, then diluted with ethyl acetate and washed successively with 5% citric acid and brine, dried and evaporated. The residue was triturated with ether and there was obtained 0.25 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-4-methyl-N-(2,4-dioxo-1,3-diazaspiro[4.5]decan-3-yl)valeramide in the form of a white solid.

Workup

  1. washThe solution was then washed with 5% citric acid solution
  2. dry with materialsaturated sodium chloride solution, dried over anhydrous magnesium sulphate
  3. customevaporated
  4. customThe residue was purified by flash chromatography on silica gel
  5. washfollowed by hexane/ethyl acetate (1:1) for the elution
  6. customThe product obtained
  7. stirringThe mixture was stirred for 1.5 hours at room temperature
  8. washwashed successively with 5% citric acid and brine
  9. customdried
  10. customevaporated
  11. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-fe2a3b1c17514a319a5eb19a4e15e235
Source dataset
uspto-grants-2001_08
Patent number
US06281363B1

Reaction notes

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