Triethylamine → Thiomorpholinecarboxylic acid ethyl ester

HRID 23210Notes

Reaction equation

HRID 23210 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][S:11][CH2:10][CH:9]1C(O)=O)([O:3][C:4](C)(C)[CH3:5])=[O:2].Cl.C(OC(=O)[C@H](CS)N)C.C(N(CC)CC)C.BrC(Br)C>C1COCC1>[CH2:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][S:11][CH2:12][CH2:13]1)=[O:2])[CH3:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 112011,1-DibromoethaneHCID 2723617Ethyl cysteinate hydrochlorideHCID 27568314-(tert-Butoxycarbonyl)thiomorpholine-3-carboxylic acid

Product 1

HCID 53680559Thiomorpholinecarboxylic acid ethyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Boc-thiomorpholine-3-carboxylic acid can also be substituted for the compound of formula (XXIV) in Reaction Scheme 7 and can be prepared in the following manner: To THF was added cysteine ethyl ester hydrochloride (1.15 g, 6.18 mmol), triethylamine (4.17 mL, 30 mmol) and dibromoethane (2.51 mL, 6.2 mmol). After stirring for 1 hour and refluxing for 16 hours, the solids were removed by filtration. The solvent was removed in vacuo and the residue was chromatographed on silica to give thiomorpholinecarboxylic acid ethyl ester (0.94 g, 87%). The ester (15.3 g, 95 mmol) was dissolved in dioxane/water (1/1) and di-t-butyldicarbonate (24 g, 110 mmol) and LiOH were added. After stirring for 3 hours, the solvent was removed in vacuo and the pH was adjusted to 3 with KHSO3 and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried (MgSO4), and the solvent was removed in vacuo to give 17.4 g (78%) 4-Boc-thiomorpholine-3-carboxylic acid: 1H NMR (CDCl3) δ 1.45 (m, 9), 2.45 (m, 1), 2.71 (m, 1). 2.93 (m, 1), 3.10 (m. 1), 3.29 (m, 1), 4.11 (m, 1), 4.19 (m, 1), 5.20 (m, 1).

Workup

  1. customcan be prepared in the following manner
  2. temperaturerefluxing for 16 hours
  3. customthe solids were removed by filtration
  4. customThe solvent was removed in vacuo
  5. customthe residue was chromatographed on silica

Sources & evidence

ORD record
ord-a4039b47d4a5467a87ff25fb54707f59
Source dataset
uspto-grants-2005_02
Patent number
US06849739B2

Reaction notes

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