Lithium Hydroxide → (2S,3R)-3-azido-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acid

HRID 1527332Notes

Reaction equation

HRID 1527332 reaction equation
C[O:2][C:3]([C@@H:5]1[C@H:9]([N:10]=[N+:11]=[N-:12])[CH2:8][CH2:7][N:6]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:4].[Li+].[OH-]>C1COCC1.O>[C:16]([O:15][C:13]([N:6]1[CH2:7][CH2:8][C@@H:9]([N:10]=[N+:11]=[N-:12])[C@H:5]1[C:3]([OH:4])=[O:2])=[O:14])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86673820O1-tert-butyl O2-methyl (2S,3R)-3-azidopyrrolidine-1,2-dicarboxylate

Product 1

HCID 86673819(2S,3R)-3-azido-1-tert-butoxycarbonyl-pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,3R)-3-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [361367-97-7] (210 mg, 0.777 mmol; Sunshine Ltd) in THF (6 mL) was added a solution of LiOH (55.8 mg, 2.33 mmol) in water (3 mL), followed by stirring at RT for 20 h. The reaction mixture was concentrated under reduced pressure and the residual aqueous phase was washed with EtOAc (3×). The water phase was adjusted to pH 2 to 3 by adding 1N aqueous HCl, followed by extraction with EtOAc (3×). The combined organics were dried (Phase separator) and concentrated in vacuo to give the crude title compound as a colorless oil. The crude product was used in the next reaction step without further purification. MS (LC/MS): 279 [M+Na]+, 200 [MH−tBu]+, 157 [MH−Boc]+; tR (HPLC conditions b): 2.77 min.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washthe residual aqueous phase was washed with EtOAc (3×)
  3. additionby adding 1N aqueous HCl
  4. extractionfollowed by extraction with EtOAc (3×)
  5. customThe combined organics were dried (Phase separator)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4c936a07879f40dc8246953a2a97cd63
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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