(Diethylamino)sulfur trifluoride → N-(tert-Butoxycarbonyl)-(2S,4R)-4-fluoroproline benzyl ester

HRID 1244200노트

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HRID 1244200 반응식
[CH2:1]([O:8][C:9](=[O:23])[C@H:10]1[CH2:14][C@H:13](O)[CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC(=O)[C@@H]1C[C@H](O)CN1C(OC(C)(C)C)=O.C(N(S(F)(F)[F:47])CC)C>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:23])[C@@H:10]1[CH2:14][C@@H:13]([F:47])[CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 10752873N-Boc-cis-4-hydroxy-L-proline methyl esterHCID 57880982(2R,4R)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate

생성물 1

HCID 68554319N-(tert-Butoxycarbonyl)-(2S,4R)-4-fluoroproline benzyl ester수율 55.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-78 °C

실험 절차

A mixture of 3 (3.6 g, 11 mmol) and N-(tert-butoxycarbonyl)-(2S,4S)-4-hydroxyproline methyl ester (0.75 g, 3.0 mmol) was dissolved in 30 mL dry CH2Cl2 under Ar(g). The solution was cooled to −78° C., and diethylaminosulfur trifluoride (DAST; 5.6 mL, 42 mmol) was than added by syringe. The mixture was stirred for an additional 45 min at −78° C. and then allowed to warm to room temperature. After 20 h, the mixture was transferred to a separatory funnel and carefully washed with 80 mL of saturated NaHCO3(aq). A considerable amount of gas was released during wash. The organic layer was washed with an additional 2×30 mL of saturated NaHCO3(aq) and 30 mL of water, dried over MgSO4(s), and concentrated to a dark oil by rotary evaporation at reduced pressure. Flash chromatography (hexanes/EtOAc 4:1) afforded 4 (1.98 g, 6.12 mmol, 55%) as an oily yellow solid.

후처리

  1. additionthan added by syringe
  2. temperatureto warm to room temperature
  3. waitAfter 20 h
  4. customthe mixture was transferred to a separatory funnel
  5. washcarefully washed with 80 mL of saturated NaHCO3(aq)
  6. washduring wash
  7. washThe organic layer was washed with an additional 2×30 mL of saturated NaHCO3(aq) and 30 mL of water
  8. dry with materialdried over MgSO4(s)
  9. concentrationconcentrated to a dark oil by rotary evaporation at reduced pressure

출처 및 근거

ORD 기록
ord-add15122b8144cbda45fc110ea6765a7
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07122521B2

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