tert-Butyl N-(4-hydroxybutyl)carbamate → N-(t-butoxycarbonyl)-4-(2-fluoro-5-bromobenzyloxy)butylamine

HRID 1066856Notes

Reaction equation

HRID 1066856 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][C:9]=1[CH2:10]Br.[C:17]([O:21][C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][OH:29])=[O:23])([CH3:20])([CH3:19])[CH3:18]>O1CCCC1>[C:17]([O:21][C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][CH2:10][C:9]1[CH:12]=[C:13]([Br:16])[CH:14]=[CH:15][C:8]=1[F:7])=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 545141tert-Butyl N-(4-hydroxybutyl)carbamateHCID 135532954-Bromo-2-(bromomethyl)-1-fluorobenzeneHCID 23665647Potassium tert-butoxide

Product 1

HCID 21196003N-(t-butoxycarbonyl)-4-(2-fluoro-5-bromobenzyloxy)butylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

In a 25 ml flask 4-(t-butoxycarbonylamino)butanol was dissolved in tetrahydrofuran (15 ml) under a nitrogen atmosphere. The solution was cooled to −40° C. and potassium tert-butoxide (1M in tetrahydrofuran, 2.14 ml, 2.14 mmol) was added slowly. The resulting mixture was stirred at −40° C. for thirty minutes. To this reaction mixture was added 2-fluoro-5-bromobenzyl bromide (521 mg, 1.94 mmol), added dropwise as a solution in tetrahydrofuran (3.5 ml). The resulting mixture was slowly warmed to 0° C. and stirred at this temperature for two hours. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was partitioned between 1 M potassium carbonate and methylene chloride. The aqueous fraction was back-extracted with methylene chloride. The organic fractions were combined and dried over sodium sulfate. The solvents were removed in vacuo. The desired intermediate was further purified by liquid chromatography.

Workup

  1. temperatureThe resulting mixture was slowly warmed to 0° C.
  2. stirringstirred at this temperature for two hours
  3. customThe reaction mixture was partitioned between 1 M potassium carbonate and methylene chloride
  4. extractionThe aqueous fraction was back-extracted with methylene chloride
  5. dry with materialdried over sodium sulfate
  6. customThe solvents were removed in vacuo
  7. customThe desired intermediate was further purified by liquid chromatography

Sources & evidence

ORD record
ord-d3a78e57ef244b938203929a695e2ad2
Source dataset
uspto-grants-2001_06
Patent number
US06245761B1

Reaction notes

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