Ammonium Chloride → tert-Butyl trans-3-Hydroxy-4-phenylpyrrolidine-1-carboxylate

HRID 2377025노트

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HRID 2377025 반응식
[CH:1]12[O:6][CH:5]1[CH2:4][N:3]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2]2.[C:14]1([Mg]Br)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH4+].[Cl-]>C1COCC1.[Cu]I>[C:10]([O:9][C:7]([N:3]1[CH2:2][C@@H:1]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@H:5]([OH:6])[CH2:4]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

참가 물질

6

반응물 3

HCID 25517Ammonium ChlorideHCID 10103880tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylateHCID 178418255HCID 178418255, 화합물

생성물 1

HCID 73553444tert-Butyl trans-3-Hydroxy-4-phenylpyrrolidine-1-carboxylate

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of 7 g (37.8 mmol) tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (prepared according to the procedure of Okada, T.; Sato, S.; Tsuji. T.; Tsushima, T.; Nakai, H.; Yoshida, T.; Matsuura, S.; Chem. Pharm. Bull. 1993, 41 (1), p. 132-133) was suspended 0.36 g (1.89 mmol; 0.05 equiv.) copper(I) iodide in 100 mL dry THF under nitrogen atmosphere. The mixture was cooled in an ice/water bath. To this mixture was added dropwise 41.6 mL (41.6 mmol; 1.1 equiv.) of a 1.0M solution of phenylmagnesium bromide in THF. The reaction mixture was stirred at 0° C. for 3 hr then warmed to room temperature. The reaction mixture was poured into 150 mL sat. aq. NH4Cl and stirred until a blue colored solution resulted. The mixture was transferred to a separatory funnel and extracted with diethyl ether (2×150 mL). The combined ether extracts were dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The resulting thick yellow oil was purified by silica gel chromatography eluting with hexanes/EtOAc (9/1) then hexanes/EtOAc (1/1). The product fractions (Rf˜0.5 in hexanes/EtOAc (1:1) were combined and evaporated under vacuum to give the product as a clear thick oil which solidified on standing. On larger scale this product could be further purified by crystallization from hexanes. 1H-NMR (CDCl3): δ: 1.45 (s, 9H), 3.2-3.4 (m, 3H), 3.65-3.95 (m, 3H), 4.37 (q, 1H, 5 Hz), 7.25 (t, 3H), 7.37 (t, 2H) ppm.

후처리

  1. temperatureThe mixture was cooled in an ice/water bath
  2. temperaturethen warmed to room temperature
  3. stirringstirred until a blue colored solution
  4. customresulted
  5. customThe mixture was transferred to a separatory funnel
  6. extractionextracted with diethyl ether (2×150 mL)
  7. dry with materialThe combined ether extracts were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under vacuum
  10. customThe resulting thick yellow oil was purified by silica gel chromatography
  11. washeluting with hexanes/EtOAc (9/1)
  12. customevaporated under vacuum

출처 및 근거

ORD 기록
ord-bd11a663bf98477887abc0ff5d47e7b3
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07468437B2

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