Ammonia → tert-butyl (2R)-2-cyanopyrrolidine-1-carboxylate

HRID 1484090Notes

Reaction equation

HRID 1484090 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@@H:9]1[C:10](O)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([N:18](CC)CC)C.C(OC(Cl)=O)C(C)C.N.FC(F)(F)C(OC(=O)C(F)(F)F)=O>ClCCl.CO.C1COCC1.CCOC(C)=O>[C:10]([C@H:9]1[CH2:13][CH2:14][CH2:15][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])#[N:18]

Participants

10

Reactant 5

HCID 222AmmoniaHCID 8471Triethylamine2×HCID 9845Trifluoroacetic anhydrideHCID 62365Isobutyl chloroformateHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 2756788tert-butyl (2R)-2-cyanopyrrolidine-1-carboxylateYield 44.1%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-25 °C

Procedure

To a solution of 2 grams (9.3 mmols) of N-Boc-D-Proline in 19 mL of dichloromethane was added 4.2 grams (42 mmols) of triethylamine. The reaction mixture was cooled to −25° C. and 2.5 grams (18.6 mmols) of iso-butylchloroformate was added dropwise. After stirring at this low temperature for 45 minutes, 0.83 grams (49 mmols) of ammonia was added to the mixture as a 7M solution in methanol. The reaction vessel was warmed slowly to ambient temperature and the solution was stirred for an additional 16 hours. After this time, the reaction mixture was evaporated to dryness and reconstituted in 200 mL of EtOAc. The organic layer was washed with four 15 mL portions of 1N HCl, dried with MgSO4 and evaporated to dryness. The crude material was immediately subjected to general procedure E using 2 grams (18.9 mmols) of triethylamine and 2.3 grams (11.16 mmols) of trifluoroacetic anhydride in 93 mL of THF. After previously described purification procedures (column chromatography, 25% EtOAc in hexanes), 0.8 grams (4.1 mmols, 44%) of the title product was recovered. 1H and 13C NMR data were identical to that reported for 28.

Workup

  1. temperatureThe reaction vessel was warmed slowly to ambient temperature
  2. stirringthe solution was stirred for an additional 16 hours
  3. customAfter this time, the reaction mixture was evaporated to dryness
  4. washThe organic layer was washed with four 15 mL portions of 1N HCl
  5. dry with materialdried with MgSO4
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-9d4cc32061a4476ea4050590c79c9d03
Source dataset
uspto-grants-2016_08
Patent number
US09421177B2

Reaction notes

Loading…