Tetrahydrofuran → tert-butyl (3R)-3-hex-5-enoylpyrrolidine-1-carboxylate

HRID 579570Notes

Reaction equation

HRID 579570 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]1)=[O:5].[CH2:19]([Mg]Br)[CH2:20][CH:21]=[CH2:22].O1CCC[CH2:26]1>>[C:4]([C@@H:6]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:7]1)(=[O:5])[CH2:22][CH2:21][CH2:20][CH:19]=[CH2:26]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 58507551(R)-Tert-butyl 3-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylateHCID 178418797HCID 178418797, compound

Product 1

HCID 66833551tert-butyl (3R)-3-hex-5-enoylpyrrolidine-1-carboxylateYield 96%

Procedure

In a 500 mL single necked round bottomed flask, a solution of tert-butyl (3R)-3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate (7.00 g, 27.1 mmol) in tetrahydrofuran (100 mL) was cooled to 0° C. and treated with 0.5 M THF solution of 3-butenylmagnesium bromide (130 mL, 65 mmol) via a pressure equalizing addition funnel over a period of 20 minutes. Once the addition was complete, the cooling bath was removed and the mixture was allowed to warm to room temperature and stir for an additional 4 h. The reaction mixture was carefully quenched with 1 N HCl (300 mL) and stirred for an additional 20 min. The aqueous layer was extracted with ethyl acetate (3×200 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated to a yellow oil. Purification of the crude product by flash column chromatography (silica gel, 10% ethyl acetate in hexanes) afforded tert-butyl (3R)-3-hex-5-enoylpyrrolidine-1-carboxylate (6.62 g; 96%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 5.73-5.69 (m, 1H), 4.99-4.91 (m, 2H), 3.61-3.42 (m, 2H), 3.13-3.05 (m, 1H), 2.50 (t, J=7.2 Hz, 2H), 2.26 (q, J=7.2 Hz, 2H), 2.11-1.90 (m, 3H), 1.38 (s, 9H); ESI MS found for C14H23NO3 m/z [154.1 (M+1-Boc)].

Workup

  1. additionaddition funnel over a period of 20 minutes
  2. additionOnce the addition
  3. customthe cooling bath was removed
  4. customThe reaction mixture was carefully quenched with 1 N HCl (300 mL)
  5. stirringstirred for an additional 20 min
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×200 mL)
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a yellow oil
  10. customPurification of the crude product by flash column chromatography (silica gel, 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-453c1d540823466a919ff6793178c870
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…