Hydrochloric Acid → diethyl (3S,4S)-1-benzylpyrrolidine-3,4-dicarboxylate

HRID 253725

반응식

HRID 253725 반응식
[CH2:1]([NH:8][CH2:9][Si](C)(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:16]([O:25][CH2:26][CH3:27])(=[O:24])/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20].F[C:29](F)(F)C(O)=O.Cl>C1COCC1.CCCCCCC>[CH2:26]([O:25][C:16]([C@H:17]1[C@H:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:9][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:29]1)=[O:24])[CH3:27]

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 353458N-[(Trimethylsilyl)methyl]benzylamineHCID 638144Diethyl fumarate

생성물 1

HCID 6558921diethyl (3S,4S)-1-benzylpyrrolidine-3,4-dicarboxylate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8900Heptane용매

실험 절차

900 g of N-Benzyl-N-trimethylsilylmethyl-amine (4654 mmol) were dissolved in 5.6 l THF at 20-25° C. 450 ml of 36% aqueous formaldehyde (5880 mmol, 1.26 equiv.) were added over 15 min, keeping the temperature between 20-25° C. After 15 min, a mixture of 760 ml diethyl fumarate (1 equiv.), 2.25 l THF and 11.2 ml trifluoroacetic acid (0.03 equiv.) was added over 15 min. The reaction mixture was stirred overnight keeping the temperature between 20-30° C. (in process control by GC). 3.5 l of 1N HCl were added, followed by 2.3 l heptane. The aqueous phase was separated and washed with 3.4 l heptane. The heptane phases were washed sequentially with 3.5 l 1N HCl. 4.5 l MTBE were added to the combined aqueous phases. 720 ml of 32% NaOHaq were added (pH 13) under vigorous stirring. The aqueous phase was separated and re-extracted with 4.5 l MTBE. The MTBE phases were washed sequentially with 2.2 l water, combined and concentrated to dryness at 45° C. to give 1.295 kg of crude (rac)-trans-N-benzyl-pyrrolidine-3,4-dicarboxylic acid diethyl ester. If required, the crude cycloadduct can be distilled.

후처리

  1. custombetween 20-25° C
  2. additionwas added over 15 min
  3. custombetween 20-30° C.
  4. customThe aqueous phase was separated
  5. washwashed with 3.4 l heptane
  6. washThe heptane phases were washed sequentially with 3.5 l 1N HCl
  7. addition4.5 l MTBE were added to the combined aqueous phases
  8. addition720 ml of 32% NaOHaq were added (pH 13) under vigorous stirring
  9. customThe aqueous phase was separated
  10. extractionre-extracted with 4.5 l MTBE
  11. washThe MTBE phases were washed sequentially with 2.2 l water
  12. concentrationconcentrated to dryness at 45° C.

출처 및 근거

ORD 기록
ord-56aeac7bf4a1403291318c15e82a0b8b
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07872141B2

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