Pivaloyl chloride → HCID 66734028, compound

HRID 1664293Notes

Reaction equation

HRID 1664293 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16](Cl)(=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18].CCN(C(C)C)C(C)C>C(Cl)Cl.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[O:13])[CH2:10][C@H:9]1[CH2:14][O:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 11275979N-Boc-trans-4-hydroxy-L-prolinol

Product 1

HCID 66734028HCID 66734028, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A colourless solution of (2S,4R)-4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (660 g; J. Org. Chem. (2003), 68, 3923-3931) in DCM (6.6 l) was cooled down to 0° C. and treated with TEA (510 ml) and, dropwise, with pivaloyl chloride (378 ml). The reaction mixture was stirred for 24 h at rt. The reaction mixture was cooled to −8° C. and treated with DIPEA (1506 ml). A solution of sulfur trioxide pyridine complex (1036 g) in DMSO (4 l) was added dropwise over 90 min. The reaction mixture was stirred at 0° C. for 1 h and was quenched with the addition of water (41). The aq. layer was extracted with Et2O/Hex (1:1; 2×1 l) and the combined org. layers were concentrated in vacuo. The residue obtained after work up (Et2O/Hex 1:1) was crystallized from Hex (2 l) affording 675 g (74%) of a colourless powder.

Workup

  1. temperatureThe reaction mixture was cooled to −8° C.
  2. stirringThe reaction mixture was stirred at 0° C. for 1 h
  3. customwas quenched with the addition of water (41)
  4. extractionThe aq. layer was extracted with Et2O/Hex (1:1; 2×1 l)
  5. concentrationlayers were concentrated in vacuo
  6. customThe residue obtained after work up (Et2O/Hex 1:1)
  7. customwas crystallized from Hex (2 l)

Sources & evidence

ORD record
ord-ebe6f7b2880149c3b73710b60facf5df
Source dataset
uspto-grants-2011_10
Patent number
US08039466B2

Reaction notes

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