Naphthalene → tert-Butyl (2-aminocyclopentyl)carbamate

HRID 1749121Notes

Reaction equation

HRID 1749121 reaction equation
[Li].C1C2C(=CC=CC=2)C=CC=1.[C:12]([O:16][C:17](=[O:35])[NH:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[NH:24]S(C1C=CC(C)=CC=1)(=O)=O)([CH3:15])([CH3:14])[CH3:13]>C(COC)OC>[C:12]([O:16][C:17](=[O:35])[NH:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[NH2:24])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 931NaphthaleneHCID 3028194LithiumHCID 72255202HCID 72255202, compound

Product 1

HCID 22667934tert-Butyl (2-aminocyclopentyl)carbamate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A mixture of lithium granules (1.52 g, 226.6 mmol) and naphthalene (10.9 g, 85.0 mmol) in dry dimethoxyethane (350 mL) were stirred at room temperature for 2 h. The deep blue solution was then cooled to 0° C., a solution of 4 (10.0 g, 28.33 mmol) in dry dimethoxyethane (40 mL) was added dropwise over 20 min. The mixture was stirred at 0° C. for 5 h. The undissolved lithium was filtered off, and 1 N HCl solution (60 mL) was added to the filtrate. The organic layer was separated and extracted with 1 N HCl (50 mL×2). The aqueous layers were combined, extracted with diethyl ether (50 mL×3), and then basified with 2 N NaOH solution to pH 12-14. The aqueous solution was extracted with ethyl acetate (50 mL×5). Organic layers were combined, dried over Na2SO4, solvent was removed under vacuum to afford rac-1 as a colorless oil, which solidified under vacuum to a white solid (4.08 g, 72%). Rf=0.31 (hexanes/EtOAc 2:1). Mp 60-62° C. IR (film) 3301, 2967, 1689, 1526, 1453, 1390, 1365, 1250, 1170, 1045, 1020, 870, 781 cm−1. 1H NMR (300 MHz, CDCl3) δ 4.48 (s, hr, 1H), 3.48 (m, 1H), 2.99 (m, 1H), 2.14 (m, 1H), 1.98 (m, 1H), 1.70 (m, 2H), 1.45 (s, 9H), 1.38 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 156.1, 78.9, 60.5, 59.4, 33.0, 30.9, 28.4, 20.7. HRMS (EI) m/z calcd for C10H21N2O2 [M+1]+ 201.1603, found 201.1632.

Workup

  1. temperatureThe deep blue solution was then cooled to 0° C.
  2. stirringThe mixture was stirred at 0° C. for 5 h
  3. filtrationThe undissolved lithium was filtered off
  4. addition1 N HCl solution (60 mL) was added to the filtrate
  5. customThe organic layer was separated
  6. extractionextracted with 1 N HCl (50 mL×2)
  7. extractionextracted with diethyl ether (50 mL×3)
  8. extractionThe aqueous solution was extracted with ethyl acetate (50 mL×5)
  9. dry with materialdried over Na2SO4, solvent
  10. customwas removed under vacuum
  11. customto afford rac-1 as a colorless oil, which

Sources & evidence

ORD record
ord-9b03ec19d4694658969ad2a5480650d3
Source dataset
uspto-grants-2015_10
Patent number
US09156778B2

Reaction notes

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