Carbon Dioxide → HCID 68350312, compound

HRID 877714Notes

Reaction equation

HRID 877714 reaction equation
[N:1]([C@H:4]1[C@@H:8]([O:9][CH3:10])[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:5]1)=[N+]=[N-].C(=O)=O>C(N(CC)CC)C.C(#N)C.CO>[NH2:1][C@H:4]1[C@@H:8]([O:9][CH3:10])[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:5]1

Participants

6

Reactant 2

HCID 280Carbon Dioxide2×HCID 92019678HCID 92019678, compound

Product 1

HCID 68350312HCID 68350312, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

(+/−)-Cis-benzyl 3-azido-4-methoxypyrrolidine-1-carboxylate (8.0 g) was resolved using the following chiral SFC conditions: column: Chiralpak AD-H 25×3 cm, 5 μm, Column Temp. 48° C., Flow rate: 140 mL/min, Mobile Phase: 65/35=CO2/1:1 MeOH:ACN (v/v) with 0.1% triethylamine, Injection Volume: 3 mL (Conc. 59.3 mg/mL), detector wavelength: 215 nm. The isolated isomers were named “Pk1” and “Pk2” in the elution order. The Pkl was collected and concentrated to afford 3.82 g of the desired (3R,4S)-enantiomeric product. 1H NMR (400 MHz, CDCl3) δ ppm 7.36 (5H, m), 5.34 (2 H, m), 3.45-3.73 (5 H, m), 3.42 (3 H, s), 3.13-3.22 (1 H, d, m), 1.28-1.31 (2 H, br s). LCMS: M+1=251, t=1.54 min. Chiral purity: 99.9% ee (chiral HPLC conditions: column: Chiralpak AD-H (25×0.46 cm, 5 μm), 60/40=CO2/1:1 MeOH:ACN (v/v) with 0.1% triethylamine, 3 mL/min, 48° C., 215 nm, 100 bar).

Workup

  1. custom48° C., Flow rate: 140 mL/min, Mobile Phase
  2. customThe Pkl was collected
  3. concentrationconcentrated
  4. customto afford 3.82 g of the desired (3R,4S)-enantiomeric product
  5. custom1=251, t=1.54 min

Sources & evidence

ORD record
ord-e8fcf6f5170b41a1a21b045e6f2298a5
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…