Water → HCID 66706655, compound

HRID 911247Notes

Reaction equation

HRID 911247 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:12])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][O:11][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=1)[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 13200309tert-butyl N-((2R)-1-hydroxypropan-2-yl)carbamate

Product 1

HCID 66706655HCID 66706655, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve (R)-(+)-2-(tert-butoxycarbonylamino)-1-propanol (1.75 mg, 10.5 mmol) in anhydrous THF (50 mL). Add sodium hydride (60% in mineral oil, 480 mg, 12 mmol) and stir at 0° C. for 30 min. Add 4-fluorobenzyl bromide (1.5 mL, 12 mmol) followed by tetrabutylammonium iodide (370 mg, 0.1 mmol) and stir for 72 h at ambient temperature. Pour the mixture into water (500 mL), extract with DCM (3×150 mL), wash with brine, dry over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give the desired intermediate as a yellow oil (2.18 g, 77%).

Workup

  1. extractionextract with DCM (3×150 mL)
  2. washwash with brine
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-91428adba07d4875880c7d8d68caf08b
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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