Sodium Chloride → [(S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-morpholin-4-yl-4-oxobutyl]carbamic acid tert-butyl ester

HRID 1811730Notes

Reaction equation

HRID 1811730 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C@H:11]([NH:15][C:16]([O:18][CH2:19][CH:20]1[C:32]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CC1C=C(C)C=C(C)N=1.[NH:66]1[CH2:71][CH2:70][O:69][CH2:68][CH2:67]1.[Cl-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][C@H:11]([NH:15][C:16]([O:18][CH2:19][CH:20]1[C:32]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[C:12]([N:66]1[CH2:71][CH2:70][O:69][CH2:68][CH2:67]1)=[O:14])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 79532,4,6-TrimethylpyridineHCID 8083MorpholineHCID 2756101(2S)-4-(((tert-butoxy)carbonyl)amino)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59224644[(S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-morpholin-4-yl-4-oxobutyl]carbamic acid tert-butyl esterYield 99.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-4-tert-Butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (150 mg, 0.341 mmol) was dissolved in N,N-dimethylformamide (1.0 ml), and then 2-3H-1,2,3-triazolo[4,5-b]pyridin-3-ol (51 mg, 0.377 mmol), O-(7-azabenzotriazole-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (148 mg, 0.377 mmol),2,4,6-trimethylpyridine (91 μl), and morpholine (45 μl, 0.512 mol) were added thereto at room temperature. After the mixture was stirred at room temperature for 16 hours, a saturated aqueous sodium chloride solution (20 ml) was added to stop the reaction. The mixture was extracted three times with ethyl acetate (20 ml). The ethyl acetate extraction solutions were combined together, and sequentially washed with a saturated aqueous sodium bicarbonate solution (20 ml) and a saturated aqueous sodium chloride solution (20 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=1:1) to yield [(S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-morpholin-4-yl-4-oxobutyl]carbamic acid tert-butyl ester (172.2 mg) as a white amorphous material.

Workup

  1. customat room temperature
  2. customthe reaction
  3. extractionThe mixture was extracted three times with ethyl acetate (20 ml)
  4. extractionThe ethyl acetate extraction solutions
  5. washsequentially washed with a saturated aqueous sodium bicarbonate solution (20 ml)
  6. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-731e25faf42c4377a9ccd787dd729e74
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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