Ammonium Chloride → (3R,4S)-tert-Butyl 3-(bis(4-Methoxyphenyl)(phenyl)Methoxy)-4-((Methylsulfonyl)oxy)pyrrolidine-1-carboxylate

HRID 2377025Notes

Reaction equation

HRID 2377025 reaction equation
[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]

Participants

6

Reactant 3

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

Product 1

HCID 73553444(3R,4S)-tert-Butyl 3-(bis(4-Methoxyphenyl)(phenyl)Methoxy)-4-((Methylsulfonyl)oxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-bd11a663bf98477887abc0ff5d47e7b3
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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