Methane → (2S,4R)-methyl 1-(2-chloroacetyl)-4-hydroxypyrrolidine-2-carboxylate

HRID 240423Notes

Reaction equation

HRID 240423 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4]1.[Cl:12][CH2:13][C:14](Cl)=[O:15].C>C1C=CC=CC=1>[Cl:12][CH2:13][C:14]([N:6]1[CH2:7][C@H:3]([OH:2])[CH2:4][C@H:5]1[C:8]([O:10][CH3:11])=[O:9])=[O:15]

Participants

5

Reactant 3

HCID 297MethaneHCID 6577Chloroacetyl chlorideHCID 114353194-Hydroxy-L-proline methyl ester hydrochloride

Product 1

HCID 14914600(2S,4R)-methyl 1-(2-chloroacetyl)-4-hydroxypyrrolidine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a suspension of Example 19A (130 g, 0.72 mol, 1 equivalent) in benzene (3.9 L), chloroacetyl chloride (81.1 g, 0.72 mol, 1 equivalent) was added dropwise at 20-25° C. The reaction mixture was refluxed for 5 hours. Then, charcoal (500 mg) was added, and the reaction mixture was hot filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure. To this crude material, methyl tert-butyl ether (650 mL) was added, and the mixture was stirred for 30 minutes. The solid was collected by filtration, and the wet cake was dried in a vacuum tray dryer for 5 hours at about 50° C. to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.9-1.96 (m, 1H), 2.08-2.19 (m, 1H), 3.36 (d, 1H, J=14.4 Hz), 3.65 (s, 3H), 3.66 (m, 2H), 4.33 (s, 2H), 4.35 (m, 1H), 5.25 (bs, 1H); MS (ESI) m/z 222 (M+H)+.

Workup

  1. temperatureThe reaction mixture was refluxed for 5 hours
  2. filtrationthe reaction mixture was hot filtered through diatomaceous earth
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. additionTo this crude material, methyl tert-butyl ether (650 mL) was added
  5. filtrationThe solid was collected by filtration
  6. customthe wet cake was dried in a vacuum tray dryer for 5 hours at about 50° C.

Sources & evidence

ORD record
ord-a3528d5f12f946f69fd2ce393c237fd0
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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