2-Chloroethyl isocyanate → (R)-1-(2-chloroethyl)-3-(tetrahydrofuran-3-yl)urea

HRID 2278951Notes

Reaction equation

HRID 2278951 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:12]1[CH2:16][CH2:15][C@@H:14]([NH2:17])[CH2:13]1.[H-].[Na+].[Cl:20][CH2:21][CH2:22][N:23]=[C:24]=[O:25]>C1COCC1>[Cl:20][CH2:21][CH2:22][NH:23][C:24]([NH:17][C@@H:14]1[CH2:15][CH2:16][O:12][CH2:13]1)=[O:25]

Participants

5

Reactant 3

HCID 160352-Chloroethyl isocyanateHCID 24758Sodium hydrideHCID 142431694-Methylbenzene-1-sulfonic acid--(3R)-oxolan-3-amine (1/1)

Product 1

HCID 90426389(R)-1-(2-chloroethyl)-3-(tetrahydrofuran-3-yl)ureaYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. suspension of (R)-(+)-tetrahydro-3-furylamine p-toluenesulfonate salt (1.00 g, 3.86 mmol) in THF (40 mL) was treated with NaH (60% in mineral oil, 0.170 g, 4.24 mmol), stirred at 0° C. for 1.5 h, treated with 2-chloroethyl isocyanate (0.362 mL, 4.24 mmol) and stirred at RT overnight as the cooling bath expired. The mixture was treated with satd. NH4Cl and water, extracted with EtOAc (2×) and the combined organics were washed with brine (2×), dried over Na2SO4 and concentrated to dryness. The residue was treated with 1:1 EtOAc/Hex and the resulting solid collected via filtration to afford (R)-1-(2-chloroethyl)-3-(tetrahydrofuran-3-yl)urea (522 mg, 70%). MS (ESI) m/z: 193.1 (M+H+).

Workup

  1. stirringstirred at RT overnight as the cooling bath
  2. additionThe mixture was treated with satd
  3. extractionNH4Cl and water, extracted with EtOAc (2×)
  4. washthe combined organics were washed with brine (2×)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. additionThe residue was treated with 1:1 EtOAc/Hex
  8. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-04827dd5ea8c41f0b553844e51c10445
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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