4-Methylmorpholine → 1-Methylethyl N-[(1R)-1-[[[(1R)-1-(6-fluoro-2-benzothiazolyl)ethyl]amino]carbonyl]-2-methylpropyl]carbamate

HRID 1531406Notes

Reaction equation

HRID 1531406 reaction equation
[CH:1]([O:4][C:5]([NH:7][C@@H:8]([C:12]([OH:14])=O)[CH:9]([CH3:11])[CH3:10])=[O:6])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:41][C:42]1[CH:53]=[CH:52][C:45]2[N:46]=[C:47]([C@H:49]([NH2:51])[CH3:50])[S:48][C:44]=2[CH:43]=1>C1(C)C=CC=CC=1>[F:41][C:42]1[CH:53]=[CH:52][C:45]2[N:46]=[C:47]([C@H:49]([NH:51][C:12]([C@H:8]([NH:7][C:5](=[O:6])[O:4][CH:1]([CH3:2])[CH3:3])[CH:9]([CH3:10])[CH3:11])=[O:14])[CH3:50])[S:48][C:44]=2[CH:43]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 51350477(R)-1-(6-fluoro-2-benzothiazolyl)ethylamine p-toluenesulfonateHCID 53692456(2R)-3-methyl-2-{[(propan-2-yloxy)carbonyl]amino}butanoic acid

Product 1

HCID 248485461-Methylethyl N-[(1R)-1-[[[(1R)-1-(6-fluoro-2-benzothiazolyl)ethyl]amino]carbonyl]-2-methylpropyl]carbamateYield 62.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

In 500 ml of toluene, 10.2 g (0.05 mol) of N-isopropoxycarbonyl-D-valine was dissolved. Thereto were dropwise added, at −5° C., 12.4 g (0.0125 mol) of N-methylmorpholine and 6.8 g (0.05 mol) of isobutyl chlorocarbonate. Thereto was added, at −5° C., 18.3 g (0.05 mol) of (R)-1-(6-fluoro-2-benzothiazolyl)ethylamine p-toluenesulfonate. A reaction and a post-treatment were conducted in the same manner as in Reference Example 1, and the suspension of a solid in toluene was filtered to collect the solid. The solid was subjected to Soxhlet extraction for 1 week, and the extract was concentrated to obtain a solid. The solid was recrystallized from xylene to obtain 11.6 g (yield: 62.7%) of isopropyl {(R)-1-[(R)-1-(6-fluorobenzothiazol-2-yl)ethylcarbamoyl]-2-methylpropyl}carbamate. The compound obtained was confirmed for the structure by IR analysis and NMR analysis in comparison with its authentic material and identified.

Workup

  1. additionThereto were dropwise added, at −5° C.
  2. additionThereto was added, at −5° C.
  3. customA reaction
  4. filtrationwas filtered
  5. customto collect the solid
  6. extractionThe solid was subjected to Soxhlet extraction for 1 week
  7. concentrationthe extract was concentrated
  8. customto obtain a solid
  9. customThe solid was recrystallized from xylene

Sources & evidence

ORD record
ord-84d0880a1b47425fafb940ac0b33cb0d
Source dataset
uspto-grants-2001_03
Patent number
US06197969B1

Reaction notes

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