Hydrochloric Acid → 1-Fluoro-5-phthalimido-2-pentanol

HRID 2163489

반응식

HRID 2163489 반응식
[C:1]1(=[O:18])[N:5]([CH2:6][CH2:7][CH2:8][C:9]([CH2:11][F:12])=[O:10])[C:4](=[O:13])[C:3]2=[CH:14][CH:15]=[CH:16][CH:17]=[C:2]12.[BH4-].[Na+].Cl>O1CCCC1.CO>[F:12][CH2:11][CH:9]([OH:10])[CH2:8][CH2:7][CH2:6][N:5]1[C:1](=[O:18])[C:2]2=[CH:17][CH:16]=[CH:15][CH:14]=[C:3]2[C:4]1=[O:13]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 13254201Fluoromethyl 3-phthalimidopropyl ketone

생성물 1

HCID 204919261-Fluoro-5-phthalimido-2-pentanol

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-20 °C

실험 절차

To a solution of 550 mg (2.2 mmole) of fluoromethyl 3-phthalimidopropyl ketone in a mixture of 5 ml of tetrahydrofuran and 5 ml of methanol cooled to -20° C is added a solution of 0.8 mmole of sodium borohydride in a mixture of 5 ml of tetrahydrofuran and 5 ml of methanol precooled to -20° C. The reaction mixture is stirred for 15 minutes at -20° C and then neutralized with 2 M HCl to a pH of 1. The solvents are evaporated under reduced pressure and the residue is partitioned between water and chloroform. The organic phase is washed with brine, dried over magnesium sulfate and concentrated to give a residue which is recrystallized from tetrahydrofuran-diethylether to afford 1-fluoro-5-phthalimido-2-pentanol, m.p. 85° C. A mixture of 264 mg (1.05 mmole) of 1-fluoro-5-phthalimido-2-pentanol, 170 mg (1.05 mmole) of the phthalimide, 302 mg (1.05 mmole) of triphenylphosphine and 201 mg (1.15 mmole) of diethylazodicarboxylate in 8 ml of tetrahydrofuran is stirred under nitrogen for 2 hours at 25° C. The solvent is evaporated under reduced pressure and the residue taken up in benzene. The insoluble material is discarded and the residue obtained after concentration of the filtrate is recrystallized from tetrahydrofuran-diethylether to give 1-fluoromethyl-1,4-butanediyl-bis-phthalimide, m.p. 112° C. A suspension of 3.1 g of 1-fluoromethyl-1,4-butanediyl-bis-phthalimide in 140 ml of concentrated HCl is heated at reflux temperature for 3 days. The phthalic acid which precipitates on cooling to 4° C is filtered off. The filtrate is concentrated to about 20 ml and cooled to 4° C. The remaining phthalic acid which separates is filtered off and the filtrate is concentrated under reduced pressure. The residue is treated with 40 ml of boiling isopropyl alcohol 3 times and then recrystallized from absolute ethanol to give 1-fluoromethyl-1,4-butanediamine dihydrochloride, m.p. 154° C.

후처리

  1. customprecooled to -20° C
  2. customThe solvents are evaporated under reduced pressure
  3. customthe residue is partitioned between water and chloroform
  4. washThe organic phase is washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a residue which
  8. customis recrystallized from tetrahydrofuran-diethylether

출처 및 근거

ORD 기록
ord-ad62d09bd3444bef9a80843e87f5c54e
출처 데이터셋
uspto-grants-1979_01
특허 번호
US04134918

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