Hydrochloric Acid → N-Nitroso-L-proline

HRID 1178760Notes

Reaction equation

HRID 1178760 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].[N:9]([O-])=[O:10].[Na+].Cl>O>[N:9]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4])=[O:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 145742L-ProlineHCID 23668193Sodium Nitrite

Product 1

HCID 10419304N-Nitroso-L-prolineYield 105%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of L-proline (2.50 kg, 21.6 moles) and sodium nitrite (2.10 kg, 30.4 moles) in water (5.0 L) maintained at 0-10° C. is added concentrated hydrochloric acid (2.53 L) and the resulting slurry is stirred for 16 hours at ambient temperature. The reaction mixture is extracted with t-butyl methyl ether (1×6 L+2×3 L) and the organic solution is concentrated using a rotary evaporator with a bath temperature below 35° C. Residual water is removed by evaporation with 2.0 L of toluene. The resulting (2S)-1-nitrosoproline (3.25 kg, 105%) is isolated as a yellow solid and dried under vacuum at 25° C., m.p. 100-102° C., HPLC purity, 96.3% (area % HPLC conditions described in Example 7) and residual toluene, 4%. The product of the example is used directly, without further purification, in the next step (see example 2).

Workup

  1. extractionThe reaction mixture is extracted with t-butyl methyl ether (1×6 L+2×3 L)
  2. concentrationthe organic solution is concentrated
  3. customa rotary evaporator with a bath temperature below 35° C
  4. customResidual water is removed by evaporation with 2.0 L of toluene

Sources & evidence

ORD record
ord-3ef9430ce5ac4e5c9d7e3d149a888979
Source dataset
uspto-grants-2007_10
Patent number
US07276611B2

Reaction notes

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