1-Butanol → (1R,4S)-1-acetylamino-4-(hydroxymethyl)-2-cyclopentene

HRID 1836945Notes

Reaction equation

HRID 1836945 reaction equation
C([C:4]12[CH2:10][CH:7]([CH:8]=[CH:9]1)[C:6](=[O:11])[NH:5]2)(=O)C.[BH4-].[Na+].[CH2:14]([OH:18])[CH2:15]CC.CCCCCC>O.CC(O)CC.CO>[C:14]([NH:5][C@@H:4]1[CH2:10][C@H:7]([CH2:6][OH:11])[CH:8]=[CH:9]1)(=[O:18])[CH3:15]

Participants

8

Reactant 4

HCID 2631-ButanolHCID 8058HexaneHCID 4311764Sodium borohydride2×HCID 23496772(-)-Acetyl-2-azabicyclo[2.2.1]hept-5-ene-3-one

Product 1

HCID 10130076(1R,4S)-1-acetylamino-4-(hydroxymethyl)-2-cyclopenteneYield 85%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6568(+-)-2-ButanolSolvent

Conditions

Temperature
1 °C

Procedure

1.3.2 287.4 g (−)-acetyl-2-azabicyclo[2.2.1]hept-5-ene-3-one (100%==>−255 ml, 97%; 1.9 moles) were dissolved in 380 ml water and 1217 ml 2-butanol. The solution was cooled to 0 to 2° C. 45 g NaBH4 (1.188 moles, 1.25 eq.) were suspended in 304 ml fresh 2 butanol in another stirring device. The NaBH4 suspension as added to the solution during 1-2 hours. The reaction was exothermic, and the temperature was not allowed to exceed 5° C. The temperature had to be at 0° C. before a portion was added. The reaction was followed by DC (thin-layer chromatography) (hexane/etrol/MeOH: 551). The reaction was allowed to continue for 1 to 2 hours after the addition. When the reaction as complete (educt concentration had to be at <1.0%), the pH was adjusted to 2 with ca. 135 g concentrated hydrochloric acid. The temperature as maintained below 10° C. The pH was then adjusted immediately to 9 with ca. 85 ml 30% sodium hydroxide solution. The precipitated salts were filtered and washed with 127 ml fresh 2-butanol. The filtrate and the “2-butanol wash” were combined, and the phases separated. The aqueous phase as extracted twice with 380 ml fresh 2-butanol each time. The 2-butanol phases were combined. Ca. 2450 g of a 10% solution of the product (1R,4S)-1-acetylamino-4-(hydroxymethyl)-2-cyclopentene, were obtained in 2-butanol. This corresponded to ca. 250 g of 100% product, (1R,4S)-1-acetylamino-4-(hydroxymethyl)-2-cyclopentene, corresponding to a yield of 85%.

Workup

  1. customto exceed 5° C
  2. customto be at 0° C. before a portion
  3. additionwas added
  4. additionafter the addition
  5. customWhen the reaction
  6. concentrationas complete (educt concentration had to be at <1.0%)
  7. temperatureThe temperature as maintained below 10° C
  8. filtrationThe precipitated salts were filtered
  9. washwashed with 127 ml fresh 2-butanol
  10. washThe filtrate and the “2-butanol wash”
  11. customthe phases separated
  12. extractionThe aqueous phase as extracted twice with 380 ml fresh 2-butanol each time

Sources & evidence

ORD record
ord-34bfc9e335f54bf7a118ffc8030a1b7e
Source dataset
uspto-grants-2004_08
Patent number
US06780634B1

Reaction notes

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