Lithium Hydroxide → 1-[(Tert-butoxy)carbonyl]-3-(methoxymethyl)pyrrolidine-3-carboxylic acid

HRID 1045357Notes

Reaction equation

HRID 1045357 reaction equation
[CH3:1][O:2][CH2:3][C:4]1([C:16]([O:18]C)=[O:17])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.[Li+].[OH-]>CO>[C:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][C:4]([CH2:3][O:2][CH3:1])([C:16]([OH:18])=[O:17])[CH2:5]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 595695741-tert-Butyl 3-methyl 3-(methoxymethyl)pyrrolidine-1,3-dicarboxylate

Product 1

HCID 595695551-[(Tert-butoxy)carbonyl]-3-(methoxymethyl)pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The title compound was prepared according to general procedure B described in connection with Scheme 2. 1-tert-Butyl 3-methyl 3-(methoxymethyl)pyrrolidine-1,3-dicarboxylate (4.5 g, 16.5 mmol) was dissolved in 30 mL of MeOH and a solution LiOH (0.79 g, 33 mmol) in 20 mL was added. The reaction mixture was microwaved at 130° C. for 25 min in 5 vials. The methanol was evaporated and the residue was acidified to pH 1-2 with KHSO4 solid. The acid was extracted with EtOAc (3×50 mL). The combined organic fractions were washed with 1N KHSO4 and with brine and then dried over Na2SO4. The solvent was evaporated to give 7.09 g of the desired acid (91% crude yield). 1H NMR (400 MHz, CDCl3): δ 10.70 (bs, 1H), 3.76 (d, 1H), 3.62-3.41 (m, 5H), 3.35 (s, 3H), 2.34-2.25 (m, 1H), 1.98-1.93 (m, 1H), 1.45 (s, 9H); MS (ESI) m/z: Calculated for C12H21NO5: 259.1. found: 260 (M+1)+.

Workup

  1. customThe reaction mixture was microwaved at 130° C. for 25 min in 5 vials
  2. customThe methanol was evaporated
  3. extractionThe acid was extracted with EtOAc (3×50 mL)
  4. washThe combined organic fractions were washed with 1N KHSO4 and with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was evaporated

Sources & evidence

ORD record
ord-d45792be0f5f423c822529d598d937f3
Source dataset
uspto-grants-2013_10
Patent number
US08569282B2

Reaction notes

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