4-Methylmorpholine → 3-Tert-butoxycarbonyl-5(S)-{2-[N-(1-carbamoyl-1-methyl-ethyl)-carbamoyl]-2(S)-isopropyl-ethyl}-4(S)-{2(S)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propyl}-2,2-dimethyl-1,3-oxazolidine

HRID 744841Notes

Reaction equation

HRID 744841 reaction equation
CN1CCOCC1.Cl.[NH2:9][C:10]([CH3:15])([CH3:14])[C:11]([NH2:13])=[O:12].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:40]([O:44][C:45]([N:47]1[C@@H:51]([CH2:52][C@@H:53]([CH:69]([CH3:71])[CH3:70])[CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[C:57]([O:63][CH2:64][CH2:65][CH2:66][O:67][CH3:68])[CH:56]=2)[C@H:50]([CH2:72][C@H:73]([C:77](O)=[O:78])[CH:74]([CH3:76])[CH3:75])[O:49][C:48]1([CH3:81])[CH3:80])=[O:46])([CH3:43])([CH3:42])[CH3:41]>CN(C)C=O>[C:40]([O:44][C:45]([N:47]1[C@@H:51]([CH2:52][C@@H:53]([CH:69]([CH3:71])[CH3:70])[CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[C:57]([O:63][CH2:64][CH2:65][CH2:66][O:67][CH3:68])[CH:56]=2)[C@H:50]([CH2:72][C@H:73]([C:77](=[O:78])[NH:9][C:10]([C:11](=[O:12])[NH2:13])([CH3:15])[CH3:14])[CH:74]([CH3:75])[CH3:76])[O:49][C:48]1([CH3:80])[CH3:81])=[O:46])([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145690092-Amino-2-methylpropanamide hydrochlorideHCID 236254795-Oxazolidinepropanoic acid, 3-[(1,1-dimethylethoxy)carbonyl]-4-[(2S)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-2,2-dimethyl-alpha-(1-methylethyl)-, (alphaS,4S,5S)-

Product 1

HCID 228657843-Tert-butoxycarbonyl-5(S)-{2-[N-(1-carbamoyl-1-methyl-ethyl)-carbamoyl]-2(S)-isopropyl-ethyl}-4(S)-{2(S)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propyl}-2,2-dimethyl-1,3-oxazolidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

106 μl of 4-methyl-morpholine, 66 mg of 2-aminoisobutyric acid amide hydrochloride and 91 mg of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) are added in succession to 119 mg of 3-tert-butoxycarbonyl-5(S)-(2(S)-carboxy-3-methyl-butyl)-4(S)-{2(S)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propyl}-2,2-dimethyl-1,3-oxazolidine (Example 124c) in 8 ml of dimethylformamide. The reaction mixture is stirred for 8 days at 40° C. The mixture is concentrated by evaporation and the residue is partitioned between ethyl acetate and saturated sodium chloride solution. The organic phases are concentrated by evaporation and the residue is purified by means of FC (60 g of silica gel, dichloromethane/methanol=95:5). The title compound is obtained: Rf (dichloromethane/methanol=95:5)=0.30.

Workup

  1. concentrationThe mixture is concentrated by evaporation
  2. customthe residue is partitioned between ethyl acetate and saturated sodium chloride solution
  3. concentrationThe organic phases are concentrated by evaporation
  4. customthe residue is purified by means of FC (60 g of silica gel, dichloromethane/methanol=95:5)

Sources & evidence

ORD record
ord-1a69636e059e465fbe9a9d14f27b186e
Source dataset
uspto-grants-1996_09
Patent number
US05559111

Reaction notes

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