Hydrochloric Acid → 1,2-Pyrrolidinedicarboxylic acid, 4-(methoxymethyl)-, 1-(1,1-dimethylethyl) ester, (2S,4S)-

HRID 2038821Notes

Reaction equation

HRID 2038821 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([C:16]([O:18]C)=[O:17])[CH2:5]1.[Li+].[OH-].Cl>C1COCC1.CO>[C:12]([O:11][C:9]([N:7]1[CH2:8][C@@H:4]([CH2:3][O:2][CH3:1])[CH2:5][C@H:6]1[C:16]([OH:18])=[O:17])=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 69675330(2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 696720591,2-Pyrrolidinedicarboxylic acid, 4-(methoxymethyl)-, 1-(1,1-dimethylethyl) ester, (2S,4S)-Yield 100.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (2.11 g, 7.7 mmol) in a mixture of THF (38 mL) and MeOH (15 mL) was added LiOH (2.5 M aqueous, 15 mL, 38.6 mmol). The resulting solution was stirred at room temperature for 2 h, and acidified with aqueous HCl (1N). The desired product was extracted with CH2Cl2 (4×). The combined organic layers were dried over Na2SO4 and concentrated to provide (2S,4S)-1-(tert-butoxycarbonyl)-4-(methoxymethyl)pyrrolidine-2-carboxylic acid (2.0 g, 99%). 1H-NMR: 400 MHz, (CDCl3) δ: (mixture of rotamers, major reported) 4.33 (t, 1H), 3.65 (m, 1H), 3.35 (m, 2H), 3.32 (s, 3H), 3.16 (t, 1H), 2.45 (m, 2H), 2.12 (m, 1H), 1.46 (s, 9H).

Workup

  1. extractionThe desired product was extracted with CH2Cl2 (4×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-e12740e8d5bf4dbaaf65b8a2e15526b0
Source dataset
uspto-grants-2013_11
Patent number
US08575135B2

Reaction notes

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