Triethylamine → HCID 68292008, compound

HRID 1408931Notes

Reaction equation

HRID 1408931 reaction equation
C(N(CC)CC)C.Cl[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].[OH:19][C@H:20]1[CH2:24][CH2:23][C@H:22]([NH:25]C2C3N(C=CC=3)N=CC=2C(N)=O)[C:21]1([CH3:39])[CH3:38].C(=O)(O)[O-].[Na+]>ClCCl>[OH:19][C@@H:20]1[CH2:24][CH2:23][C@H:22]([NH:25][C:9](=[O:10])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:21]1([CH3:39])[CH3:38]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 68291321HCID 68291321, compound2×

Product 1

HCID 68292008HCID 68292008, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (6.69 mL, 48.0 mmol) and benzyl chloroformate (4.22 g, 24.71 mmol) were added to a solution of 3-amino-2,2-dimethylcyclopentanol (3.10 g, 23.99 mmol, from Step 3 of Intermediates 15 and 16) in dichloromethane (100 mL) at 0° C. The resulting mixture was stirred at room temperature for 15 h, treated with saturated sodium bicarbonate (50 mL) and extracted with dichloromethane (3×150 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated. Silica gel chromatography, eluting with 0 to 40% ethyl acetate in hexanes, gave separation of the two major components. The first eluted product was found to be benzyl cis-3-hydroxy-2,2-dimethylcyclopentylcarbamate (cis-isomer B, 640 mg, 10% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 7.13-7.53 (5 H, m), 5.06 (2 H, s), 3.53-3.86 (2 H, m), 1.81-2.05 (2 H, m), 1.36-1.71 (2 H, m), 0.86-1.07 (3 H, m), 0.78 (3 H, s); MS (ES+) m/z: 264.2 (M+H); HPLC retention time: 2.32 min (analytical HPLC Method A). The second eluted product was benzyl trans-3-hydroxy-2,2-dimethylcyclopentylcarbamate (trans-isomer A, 1.77 g, 28% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 7.21-7.51 (5 H, m), 5.06 (2 H, s), 3.91 (1 H, t, J=8.25 Hz), 3.64-3.79 (1 H, m), 1.99-2.20 (2 H, m), 1.33-1.62 (2 H, m), 0.94 (3 H, s), 0.79 (3 H, s); MS (ES+) m/z: 264.3 (M+H); HPLC retention time: 2.29 min (analytical HPLC Method A).

Workup

  1. extractionextracted with dichloromethane (3×150 mL)
  2. washThe combined organic extracts were washed with water (50 mL), brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0 to 40% ethyl acetate in hexanes
  7. customgave
  8. customseparation of the two major components

Sources & evidence

ORD record
ord-42b1a58b650740d99592e05ba256d305
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

Loading…