Ethyl orthoformate → HCID 90402410, compound

HRID 1854736Notes

Reaction equation

HRID 1854736 reaction equation
[CH:1]1([C:4]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])([CH3:9])/[C:5](=[N:7]/[OH:8])/[NH2:6])[CH2:3][CH2:2]1.[CH2:17](OC(OCC)OCC)C>CC(O)=O>[CH:1]1([C:4]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])([C:5]2[N:6]=[CH:17][O:8][N:7]=2)[CH3:9])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 90402488HCID 90402488, compound

Product 1

HCID 90402410HCID 90402410, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

(Z)-2-cyclopropyl-2-((R)-1,1-dimethylethylsulfinamido)-N′-hydroxypropanimidamide (321 mg, 1.30 mmol) in triethoxymethane (2.0 ml, 12 mmol) was treated with AcOH (2 ml) at rt. The reaction was allowed to stir at rt for 16 h. LCMS showed a major peak with the expected M+H. The reaction was concentrated to dryness azeotroping with toluene 2×. The resulting yellow oil was purified on silica gel (Biotage, EtOAc/hexanes gradient (Rf ˜0.2 in 70% EtOAc/Hex, visualized with permanganate stain), to give the expected product (first eluting diastereomer, 120 mg, 0.466 mmol, 36% yield) consistent by LCMS and NMR. LC-MS retention time: 1.21 min; m/z M+H: 258. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (500 MHz, DMSO-d6) δ 9.53 (s, 1H), 5.29 (s, 1H), 1.53-1.49 (m, 1H), 1.47 (s, 3H), 1.10 (s, 9H), 0.49-0.40 (m, 4H).

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. customazeotroping with toluene 2×
  3. customThe resulting yellow oil was purified on silica gel (Biotage, EtOAc/hexanes gradient (Rf ˜0.2 in 70% EtOAc/Hex, visualized with permanganate stain)

Sources & evidence

ORD record
ord-a3283d27a10c4bbfa7b25a72bcb91e36
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

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