Di-tert-butyl dicarbonate → HCID 69371147, compound

HRID 1372464Notes

Reaction equation

HRID 1372464 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[N:28][C:29]([O:32]C)=[CH:30][CH:31]=2)=[CH:22][CH:21]=1)[CH3:19])[C:10]([N:12]1[CH2:16][CH2:15][C@H:14]([F:17])[CH2:13]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+].C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>O1CCOCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29](=[O:32])[NH:28][CH:27]=2)=[CH:22][CH:21]=1)[CH3:19])[C:10]([N:12]1[CH2:16][CH2:15][C@H:14]([F:17])[CH2:13]1)=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 69372943HCID 69372943, compound

Product 1

HCID 69371147HCID 69371147, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

(3S)-1-[(2S,3S)-2-(tert-Butoxycarbonylamino)-3-[4-(6-methoxypyridin-3-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine from Example 5, Step A (0.65 g, 1.42 mmol) was mixed with pyridine hydrochloride (2.25 g, 19.5 mmol) neat and placed in a preheated oil bath (160° C.). After stirring at 160° C. for 20 min, the reaction was cooled to room temperature and neutralized to pH 7 with saturated sodium bicarbonate solution. To this was added 15 mL of 1,4-dioxane followed by di-tert-butyldicarbonate (2.14 g, 9.82 mmol). After stirring at room temperature for 12 h, the reaction was partitioned between ethyl acetate and saturated aqueous brine. The organic layer was separated, and the aqueous layer was extracted with two portions of ethyl acetate. The combined organic layers were dried over sodium sulfate and the solvents removed by evaporation under diminished pressure. Purification by preparative TLC (silica, 50% ethyl acetate/hexanes) afforded the desired product.

Workup

  1. customplaced in a preheated oil bath
  2. custom(160° C.)
  3. stirringAfter stirring at room temperature for 12 h
  4. customthe reaction was partitioned between ethyl acetate and saturated aqueous brine
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with two portions of ethyl acetate
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. customthe solvents removed by evaporation under diminished pressure
  9. customPurification by preparative TLC (silica, 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c9d152fdd909478ab8024914b105bf5a
Source dataset
uspto-grants-2007_01
Patent number
US07157490B2

Reaction notes

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