Bromide ion → (1R,5S)-tert-Butyl-3-pent-4-enoyl-8-azabicyclo[3.2.1]-octane-8-carboxylic acid

HRID 1778578Notes

Reaction equation

HRID 1778578 reaction equation
CON(C)[C:4]([CH:6]1[CH2:12][CH:11]2[N:13]([C:14]([O:16]C(C)(C)C)=[O:15])[CH:8]([CH2:9][CH2:10]2)[CH2:7]1)=[O:5].[Br-].O.Cl>O1CCCC1>[C:6]([C@@:11]12[N:13]([C:14]([OH:16])=[O:15])[C@@H:8]([CH2:9][CH2:10]1)[CH2:7][CH:6]([C:4](=[O:5])[CH2:11][CH2:10][CH:9]=[CH2:8])[CH2:12]2)([CH3:12])([CH3:7])[CH3:4]

Participants

6

Reactant 4

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 962WaterHCID 89514318Tert-butyl 3-(methoxy(methyl)carbamoyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 117700454(1R,5S)-tert-Butyl-3-pent-4-enoyl-8-azabicyclo[3.2.1]-octane-8-carboxylic acidYield 173.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

While under a nitrogen atmosphere, a solution of tert-butyl 3-(methoxy(methyl)carbamoyl)-8-azabicyclo[3.2.1]octane-8-carboxylate (1.7 g, 5.7 mmol), in tetrahydrofuran (25 mL) was cooled to 0° C. and treated with 3-butenylmagnesiun bromide (0.5 M in THF, 28.5 mL, 14.3 mmol) in a drop wise manner. The solution was stirred for 1 hour at 0° C. then allowed to warm to room temperature overnight. The resulting solution was poured into water, acidified to pH 3-4 with 1 N hydrochloric acid, and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane) gave (1R,5S)-tert-Butyl-3-pent-4-enoyl-8-azabicyclo[3.2.1]-octane-8-carboxylic acid as a colorless oil (1.45 g, 87%); 1H NMR (CDCl3, 400 MHz) δ 5.81 (m, 1H), 5.01 (m, 2H), 4.29 (br s, 2H), 2.83 (m, 1H), 2.53 (t, J=7.5 Hz, 1H), 2.32 (q, J=7 Hz, 2H), 2.03 (m, 2H), 1.83 (t, J=12.5 Hz, 2H), 1.60-1.71 (m, 5H) and 1.48 (s, 9H); m/z for C17H27NO3 expected 293.2. found 316.3 (M+Na)+, 294.3 (M+H)+.

Workup

  1. temperatureto warm to room temperature overnight
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-2d94f7dca4284bd79e7e9a10132c6a0d
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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