Thionyl Chloride → alpha-Chloro-2-nitrobenzenepropanoic acid 2,6-dimethylpiperidine salt

HRID 4738

Reaction equation

HRID 4738 reaction equation
S(Cl)(Cl)=O.C[N+](C)=C[Cl:8].[Cl-].O[CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N+:23]([O-:25])=[O:24])[C:13]([OH:15])=[O:14].[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH:29]([CH3:33])[NH:28]1>ClCCl.CCOCC.C(O)C.CN(C)C=O>[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH:29]([CH3:33])[NH:28]1.[Cl:8][CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N+:23]([O-:25])=[O:24])[C:13]([OH:15])=[O:14]

Participants

9

Reactant 4

HCID 24386Thionyl ChlorideHCID 68843NanofinHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 136517582-Hydroxy-3-(2-nitrophenyl)propanoic acid

Product 1

HCID 13651760alpha-Chloro-2-nitrobenzenepropanoic acid 2,6-dimethylpiperidine salt

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To magnetically stirred N,N-dimethylformamide (3 mL) cooled in ice was added slowly dropwise thionyl chloride (4.5 ml., 61.7 mmol) and the resulting cold Vilsmeier reagent was diluted with dichloromethane (30 ml.). (-)-α-Hydroxy-2-nitrobenzenepropanoic acid [3.00 g., 14.2 mmol, [α]D25 -63.04° (c 0.955, 95% ethanol)] in dichloromethane (70 ml.) was added. The resulting solution, protected from moisture, was left at room temperature (25° overnight. The solution was added to stirred ice and the mixture was stirred for 1 hour, during which time it warmed to room temperature. The dichloromethane solution was separated and washed thrice with water and dried (MgSO4). Evaporation gave a syrup which was subjected to an oil pump vacuum for 1.5 hours. The syrup was dissolved in ether and 2,6-dimethylpiperidine was added to approximate neutrality (pH 9 with pH paper). The crude titled product [2.98 g. (61%), m.p. 155°-158° C. dec.] crystallized readily. Two crystallizations (methanol-ether) with decolorization (Nuchar C-190N) gave 1.91 g. (39%) of pure product; m.p. 164°-167° C. dec., [α]D25 +42.11° (c 1.09, 95% ethanol).

Workup

  1. additionThe solution was added
  2. stirringthe mixture was stirred for 1 hour, during which time it
  3. customThe dichloromethane solution was separated
  4. washwashed thrice with water
  5. dry with materialdried (MgSO4)
  6. customEvaporation
  7. customgave a syrup which
  8. waitwas subjected to an oil pump vacuum for 1.5 hours
  9. customThe crude titled product [2.98 g. (61%), m.p. 155°-158° C. dec.] crystallized readily
  10. customTwo crystallizations (methanol-ether) with decolorization (Nuchar C-190N)
  11. customgave 1.91 g

Sources & evidence

ORD record
ord-4fa3d32004a64365b5c133d511bd3d13
Source dataset
uspto-grants-1988_02
Patent number
US04727183

Linked notes

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