Carbon Dioxide → HCID 86758302, compound

HRID 2227380Notes

Reaction equation

HRID 2227380 reaction equation
[C:1]([C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([OH:3])=O.[C:16](=O)=[O:17].C([N:21]([CH2:24]C)CC)C.C(Cl)(=O)C(C)(C)C.Cl.CNOC.Cl>ClCCl>[CH3:16][O:17][CH2:24][NH:21][C:1]([C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:3]

Participants

8

Reactant 6

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 86758302HCID 86758302, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

13.0 g (56.8 mmol) of 1,1-dimethylethyl (R)-2-carboxypyrrolidine-1-carboxylate and 190 ml of dichloromethane are placed in a 500 ml three-necked flask fitted with a thermometer and a 250 ml addition funnel. The mixture is cooled to −20° C. on a bath of cardice and 7.91 ml (57 mmol) of triethylamine are added, followed by 7.01 ml (56.8 mmol) of pivaloyl chloride. The mixture is stirred vigorously for 15 minutes at −10° C., the temperature is then allowed to rise to 0° C., and a solution of 11.07 g (113 mmol) of N,O-dimethylhydroxylamine hydrochloride and 17.4 ml (125 mmol) of triethylamine in 160 ml of dichloromethane is added dropwise. The reaction mixture is allowed to warm to room temperature over 120 minutes and is then cooled to 0° C. on an ice bath and 100 ml of a 0.1N hydrochloric acid solution are added. The organic phase is washed successively with 100 ml of 0.2M sodium hydroxide solution and with 200 ml of brine, and is then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on a column of silica (elution solvent: 50% ethyl acetate in cyclohexane). 14.26 g (yield: 92%) of 1,1-dimethylethyl (R)-2-[(methoxymethylamino)carbonyl]pyrrolidine-1-carboxylate are obtained in the form of a colorless oil.

Workup

  1. customfitted with a thermometer and a 250 ml addition funnel
  2. additionare added
  3. customto rise to 0° C.
  4. temperatureto warm to room temperature over 120 minutes
  5. temperatureis then cooled to 0° C. on an ice bath
  6. washThe organic phase is washed successively with 100 ml of 0.2M sodium hydroxide solution and with 200 ml of brine
  7. dry with materialis then dried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue is purified by chromatography on a column of silica (elution solvent: 50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-fed2e53e34f24cb19dd0300cf34e3334
Source dataset
uspto-grants-2002_07
Patent number
US06413984B1

Reaction notes

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