1-Chloroethyl chloroformate → (S)-2-(4-bromophenyl)morpholine hydrochloride

HRID 2063346Notes

Reaction equation

HRID 2063346 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H](C3C=CC=CC=3)C)[CH2:9]2)=[CH:4][CH:3]=1.[Cl:22]C(OC(Cl)C)=O>ClCCCl>[ClH:22].[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][NH:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 50992522(2S)-2-(4-bromophenyl)-4-[(1R)-1-phenylethyl]morpholine2×

Product 1

HCID 66842433(S)-2-(4-bromophenyl)morpholine hydrochlorideYield 93.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (intermediate 13, 50.0 g, 144 mmol) in 1,2-dichloroethane (240 ml) was added 1-chloroethyl chloroformate (103 g, 722 mmol) at room temperature. The mixture was refluxed for 8 hours. The mixture was concentrated under reduced pressure and methanol (120 ml) was added. The mixture was refluxed for 3 hours, and was concentrated under reduced pressure to afford the crude product. This crude product was washed with acetone, dried under reduced pressure to afford (2S)-2-(4-bromophenyl)morpholine hydrochloride (intermediate 14, 37.6 g, 93%).

Workup

  1. temperatureThe mixture was refluxed for 8 hours
  2. concentrationThe mixture was concentrated under reduced pressure and methanol (120 ml)
  3. additionwas added
  4. temperatureThe mixture was refluxed for 3 hours
  5. concentrationwas concentrated under reduced pressure
  6. customto afford the crude product
  7. washThis crude product was washed with acetone
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-25a969bbe1344022a6023858ddf407bf
Source dataset
uspto-grants-2012_10
Patent number
US08288383B2

Reaction notes

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