Thiazole → Tert-butyl 3-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]pyrrolidine-1-carboxylate

HRID 2272674Notes

Reaction equation

HRID 2272674 reaction equation
[Cl-].[Li+].C([Mg]Cl)(C)C.[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[C:13]([CH:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1)(=[O:15])[CH3:14]>O1CCCC1.[Cl-].[NH4+]>[OH:15][C:13]([CH:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17]1)([C:9]1[S:8][CH:12]=[CH:11][N:10]=1)[CH3:14]

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 25257021tert-Butyl 3-acetylpyrrolidine-1-carboxylateHCID 178461733HCID 178461733, compound

Product 1

HCID 86715345Tert-butyl 3-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

Isopropylmagnesium chloride lithium chloride (1.3 M in tetrahydrofuran, 0.6 mL, 0.780 mmol) was added dropwise at room temperature to a flask containing a solution of thiazole (0.050 mL, 0.705 mmol) in tetrahydrofuran (5 mL) with a water bath around the flask. After 40 min, tert-butyl 3-acetylpyrrolidine-1-carboxylate (160 mg, 0.750 mmol) in tetrahydrofuran (5 mL) was added dropwise. After stirring at room temperature for 35 min, the mixture was diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexane) to afford tert-butyl 3-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]pyrrolidine-1-carboxylate as a 1:1 mix of diastereomers. 1H NMR (500 MHz, CDCl3) δ 7.69-7.55 (m, 1H, two sets of doublets overlap from two diastereomers), 7.23-7.14 (m, 1H, two sets of doublets overlap from two diastereomers), 3.59-2.98 (m, 4H), 2.80-2.60 (m, 1H), 1.98-1.70 (m, 2H), 1.59 (s, 3H), 1.45-1.30 (m, 9H, two sets of peaks overlap from two diastereomers).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-257276715a7c4f6cb865c39c6e2702a2
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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