4-Methylmorpholine → (9H-fluoren-9-yl)methyl tert-butyl (4-hydroxybutane-1,3-diyl)(S)-dicarbamate

HRID 1811734Notes

Reaction equation

HRID 1811734 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](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.CN1CCOCC1.[BH4-].[Na+]>O1CCCC1.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:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=2[C:27]2[C:32]1=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:17])[CH2:12][OH:13])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2756101(2S)-4-(((tert-butoxy)carbonyl)amino)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)butanoic acidHCID 4311764Sodium borohydride

Product 1

HCID 59224663(9H-fluoren-9-yl)methyl tert-butyl (4-hydroxybutane-1,3-diyl)(S)-dicarbamateYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(S)-4-tert-Butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (493 mg, 1.12 mmol) was dissolved in tetrahydrofuran (1 ml), and then isobutyl chloroformate (0.15 ml, 1.14 mmol) and N-methylmorpholine (0.125 ml, 1.15 mmol) were added thereto at −15° C. After stirring for one hour, the precipitate was filtrated and washed with tetrahydrofuran (7 ml). The filtrate was cooled to −15° C., and an aqueous solution (4 ml) of sodium borohydride (127 mg, 3.36 mmol) was dropwise added thereto. After stirring for 30 minutes, water (25 ml) was added to the solution and extracted three times with ethyl acetate (20 ml). The 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: dichloromethane:methanol=50:1) to yield [(S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-hydroxybutyl]carbamic acid tert-butyl ester (411 mg) as a colorless oily material.

Workup

  1. customat −15° C
  2. filtrationthe precipitate was filtrated
  3. washwashed with tetrahydrofuran (7 ml)
  4. stirringAfter stirring for 30 minutes
  5. extractionextracted three times with ethyl acetate (20 ml)
  6. dry with materialThe 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: dichloromethane:methanol=50:1)

Sources & evidence

ORD record
ord-8d284bd4596148979d2ce71ce1ca6972
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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