Sodium Bicarbonate → (2R,4R)-4-Azido-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester
Reaction equation
[BH4-].[Li+].C[O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([N:12]=[N+:13]=[N-:14])[CH2:9][N:8]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O.C(=O)(O)[O-].[Na+]>CCOCC>[C:18]([O:17][C:15]([N:8]1[CH2:9][C@H:10]([N:12]=[N+:13]=[N-:14])[CH2:11][C@@H:7]1[CH2:5][OH:4])=[O:16])([CH3:21])([CH3:20])[CH3:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -70 °C
Procedure
Add lithium borohydride (8.50 g, 351 mmol) to a solution of (2R,4R)-4-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (95 g, 351 mmol) in ether (1 L) at −30° C. under nitrogen. Allow the temperature to rise to 0° C. over 1.5 h and stir for an additional 2 h. Cool to −70° C. and add saturated aqueous sodium bicarbonate (1 L) dropwise. Allow to warm to room temperature, separate the layers and extract the aqueous layer with ether (1 L). Combine the ether layers, dry over sodium sulfate, filter, and concentrate. Dry the resulting material under high vacuum to obtain a yellow oil (82 g, 96%). [α]D20+20.3 (c=1.0 in methanol). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 1.99 (br s, 1H, OH), 2.20 (m, 1H), 3.34 (m, 1H), 3.50-3.78 (m, 1H), 4.29 (m, 1H), 4.78 (m, 1H).
Workup
- temperatureto warm to room temperature
- customseparate the layers
- extractionextract the aqueous layer with ether (1 L)
- dry with materialCombine the ether layers, dry over sodium sulfate
- filtrationfilter
- concentrationconcentrate
- customDry the resulting material under high vacuum
Sources & evidence
- ORD record
- ord-a166316af83d415ea0c7f72ca0c595a8
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658638B2
Reaction notes
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