Hydrochloric Acid → (R)-tert-butyl 1-(2-adamantylcarbamoyl)pyrrolidin-3-ylcarbamate

HRID 72134Notes

Reaction equation

HRID 72134 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.CCN(C(C)C)C(C)C.[CH:23]12[CH2:32][CH:27]3[CH2:28][CH:29]([CH2:31][CH:25]([CH2:26]3)[CH:24]1[N:33]=[C:34]=[O:35])[CH2:30]2.Cl>C(Cl)Cl>[CH:25]12[CH2:31][CH:29]3[CH2:28][CH:27]([CH2:32][CH:23]([CH2:30]3)[CH:24]1[NH:33][C:34]([N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:2]1)=[O:35])[CH2:26]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 128826302-Isocyanatoadamantane

Product 1

HCID 66884555(R)-tert-butyl 1-(2-adamantylcarbamoyl)pyrrolidin-3-ylcarbamateYield 19.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A vial was charged with (R)-tert-butyl pyrrolidin-3-ylcarbamate (21 mg, 0.11 mmol) and i-Pr2NEt (0.025 mL, 0.14 mmol). A solution of 2-adamantyl isocyanate (25 mg, 0.14 mmol) in CH2Cl2 (2 mL) was added with stirring. After stirring overnight the mixture was applied to a 10-mL ChemElut cartridge that had been prewetted with 5% aq HCl (6 mL). The cartridge was eluted with ether (20 mL). The eluate was evaporated to dryness and the residue was applied to a 2-g silica SPE cartridge. The cartridge was eluted sequentially with 0, 10, 25, 50, 75 and 100% EtOAc in hexanes (15 mL of each) to afford six fractions. Fractions 4 and 5 were pooled and concentrated to afford (R)-tert-butyl 1-(2-adamantylcarbamoyl)pyrrolidin-3-ylcarbamate (7.9 mg, 15%). LC-MS Method 1, tR=1.83 min, m/z=364; 1H NMR (CDCl3) 1.42 (s, 9H), 1.60-1.95 (15H), 2.17 (m, 1H), 3.21 (m, 1H), 3.46 (m, 2H), 3.61 (m, 1H), 3.96 (m, 1H), 4.22 (1H), 4.53 (d, 1H), 4.72 (1H)

Workup

  1. stirringAfter stirring overnight the mixture
  2. washThe cartridge was eluted with ether (20 mL)
  3. customThe eluate was evaporated to dryness
  4. washThe cartridge was eluted sequentially with 0, 10, 25, 50, 75 and 100% EtOAc in hexanes (15 mL of each)
  5. customto afford six fractions
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-149334d4c7ae468693f0ec4f4cae3396
Source dataset
uspto-grants-2014_09
Patent number
US08828985B2

Reaction notes

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