Benzyl chloroformate → Benzyl trans-3-azido-4-fluoro-pyrrolidine-1-carboxylate

HRID 928193Notes

Reaction equation

HRID 928193 reaction equation
[N:1]([C@H:4]1[C@H:8]([F:9])[CH2:7][NH:6][CH2:5]1)=[N+:2]=[N-:3].CCN(C(C)C)C(C)C.[C:19](Cl)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>C(Cl)Cl>[N:1]([C@H:4]1[C@H:8]([F:9])[CH2:7][N:6]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:5]1)=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 118073556(trans)-3-Azido-4-fluoropyrrolidine

Product 1

HCID 57970079Benzyl trans-3-azido-4-fluoro-pyrrolidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of (trans)-3-azido-4-fluoropyrrolidine (18 g) in CH2Cl2 (120 mL) was added DIPEA (35 g, 0.27 mol, 2.5 eq), then CBZ-Cl (22 g, 0.13 mol) was added dropwise at 0-5° C. After addition, the resulting mixture was stirred at rt overnight. The mixture was washed with sat. aq. NH4Cl (150 mL), sat. aq. NaHCO3 (3×40 mL) and brine (40 mL). The organic layer was concentrated and purified by column (petroleum ether/EtOAc=10:1˜5:1) to give the title compound (30 g, ˜100% yield in two steps, containing residual EtOAc and DCM) as a light yellow oil.

Workup

  1. additionAfter addition
  2. washThe mixture was washed with sat. aq. NH4Cl (150 mL), sat. aq. NaHCO3 (3×40 mL) and brine (40 mL)
  3. concentrationThe organic layer was concentrated
  4. custompurified by column (petroleum ether/EtOAc=10:1˜5:1)

Sources & evidence

ORD record
ord-76613ed904d642f18b18e108a99a5b4f
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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