4-Methylmorpholine → HCID 54318947, compound

HRID 1978283Notes

Reaction equation

HRID 1978283 reaction equation
[Br-].[C:2]1([P+:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:9][C:10]#[N:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N([CH2:29][CH3:30])CC)C.[C:31]([O:35][C:36]([NH:38][C@H:39]([C:51](O)=[O:52])[CH:40](CC1C=CC=CC=1)C(O)=O)=[O:37])([CH3:34])([CH3:33])[CH3:32].[CH3:54]N1CCOCC1.[CH2:61]([O:65][C:66](Cl)=[O:67])[CH:62]([CH3:64])[CH3:63].C(C[PH4])#N>C1COCC1>[CH2:61]([O:65][C:66](=[O:67])[CH2:40][CH:39]([NH:38][C:36]([O:35][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:37])[C:51](=[O:52])[C:9]([C:10]#[N:11])=[P:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:62]1[CH:64]=[CH:30][CH:29]=[CH:54][CH:63]=1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 11811037(Cyanomethyl)triphenylphosphonium bromideHCID 14032956HCID 14032956, compoundHCID 178511461HCID 178511461, compound

Product 1

HCID 54318947HCID 54318947, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of triphenyl cyanomethyl phosphonium bromide (1, 0.68 g, 1.8 mmol) in anhydrous THF (10 mL) cooled in an ice bath was added triethylamine (396 mg, 546 μL, 3.9 mmol) and the mixture stirred in an ice bath for 15 min. To a solution of N-t-butyloxycarbonyl-β-benzylaspartic acid (2, 575 mg, 1.8 mmol) in THF (15 mL) cooled to −15° C. was added N-methyl morpholine (180 mg, 196 μL, 1.8 mmol) followed by iso-butylchloroformate (243 mg, 231 μL, 1.8 mmol). The resulting solution was stirred at −15° C. for 5 min before being added dropwise with stirring to the previously prepared cyanomethylphosphorane solution. The mixture was stirred at 0° C. for 15 min and then allowed to warm to room temperature and then stirred for a further 16 h. The precipitate was removed by filtration and the solvent removed under reduced pressure. The mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane) to yield the product as a clear oil which solidified on drying (0.76 g, 70%): mp 42-44° C.; 1H NMR (CDCl3) δ1.39 (s, 9H, Boc CH3's), 2.99 (d, 2H, β-CH2), 5.06 (m, 3H, α-CH & benzyl CH2), 5.62 (d, 1H, NH), 7.28 (m, 5H, benzyl aromatic CH's), 7.52 (m, 15H, PPh3 aromatic CH's); MS (El, calculated for C36H35N2O5P, 606.2284) m/e 606.2292 (M+).

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe resulting solution was stirred at −15° C. for 5 min
  3. additionbefore being added dropwise
  4. stirringThe mixture was stirred at 0° C. for 15 min
  5. stirringstirred for a further 16 h
  6. customThe precipitate was removed by filtration
  7. customthe solvent removed under reduced pressure
  8. customThe mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-a8a2da7fa13d40e98d91a279cdb7962c
Source dataset
uspto-grants-2001_05
Patent number
US06235929B1

Reaction notes

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