1,3-Propanedithiol → 6,10-Dithia-2-aza-spiro[4.5]decane-2,3-dicarboxylic acid-2-benzyl ester 3-methyl ester

HRID 2361573Notes

Reaction equation

HRID 2361573 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][C:8](=O)[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:4].[CH2:21]([SH:25])[CH2:22][CH2:23][SH:24]>C(Cl)Cl>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][C:8]2([S:25][CH2:21][CH2:22][CH2:23][S:24]2)[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:4]

Participants

4

Reactant 2

HCID 80131,3-PropanedithiolHCID 133736081-Benzyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 140362526,10-Dithia-2-aza-spiro[4.5]decane-2,3-dicarboxylic acid-2-benzyl ester 3-methyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ketone 2 (250 mg) in CH2Cl2 at 15° C. was treated with 1,3-propanedithiol (100 uL) dropwise followed by BF3OEt2 (119 uL). The mixture was warmed to room temperature and stirred overnight. The reaction was quenched by adding 1 mL potassium carbonate aqueous solution (2 g/30 mL) followed by 321 uL of saturated sodium bicarbonate to adjust to pH 7-8. Washed organics with water, brine, then dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification on a plug of silica gel eluting with toluene→hexane/ethyl ether (2:3→0:1) yielded 200 mg (60%) of desired 6,10-dithia-2-aza-spiro[4.5]decane-2,3-dicarboxylic acid-2-benzyl ester 3-methyl ester 26 as a clear oil. 1H NMR (CDCl3) δ 7.30 (m, 5H), 5.05-5.25 (m, 2H), 4.6 (t, 0.5H), 4.55 (t, 0.5H), 3.8 (s, 1.5H), 3.75 (m, 1H), 3.6 (s, 1.5H), 2.95 (m, 1H), 2.85 (m, 3H), 2.75 (m, 1H), 2.4 (m, 0.5H), 2.35 (m, 0.5H), 2.0 (m, 2H) ppm.

Workup

  1. customThe reaction was quenched
  2. additionby adding 1 mL potassium carbonate aqueous solution (2 g/30 mL)
  3. dry with materialWashed organics with water, brine, then dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification on a plug of silica gel eluting with toluene→hexane/ethyl ether (2:3→0:1)

Sources & evidence

ORD record
ord-d3eb727088884612846bea6ba6172aa3
Source dataset
uspto-grants-2014_04
Patent number
US08691758B2

Reaction notes

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