Sodium Hydroxide → tert-butyl (2S)-2-[(4-{[(3,4-dichlorophenyl)amino]-carbonyl}piperazin-1-yl)methyl]morpholine-4-carboxylate

HRID 603201Notes

Reaction equation

HRID 603201 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O[CH2:24][C@@H:25]1[O:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1.S([O-])([O-])(=O)=S.[Na+].[Na+].Cl.[Cl:46][C:47]1[CH:48]=[C:49]([NH:54][C:55]([N:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)=[O:56])[CH:50]=[CH:51][C:52]=1[Cl:53].C(N(CC)C(C)C)(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[Cl:46][C:47]1[CH:48]=[C:49]([NH:54][C:55]([N:57]2[CH2:62][CH2:61][N:60]([CH2:24][C@@H:25]3[O:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:26]3)[CH2:59][CH2:58]2)=[O:56])[CH:50]=[CH:51][C:52]=1[Cl:53]

Participants

9

Reactant 7

HCID 14798Sodium HydroxideHCID 24477Sodium ThiosulfateHCID 81531DiisopropylethylamineHCID 159087TriacetoxyperiodinaneHCID 1512576(R)-N-Boc-2-hydroxymethylmorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 46743200N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochloride

Product 1

HCID 57656853tert-butyl (2S)-2-[(4-{[(3,4-dichlorophenyl)amino]-carbonyl}piperazin-1-yl)methyl]morpholine-4-carboxylateYield 24.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dess-Martin periodinane (8.60 g) was added to tert-butyl (2R)-2-(hydroxymethyl)morpholine-4-carboxylate (4.00 g) in dry DCM at 0° C. The reaction was warmed to RT and stirred for a further 2 h. Aqueous sodium thiosulfate (10% w/v, 50 ml) was added and the DCM layer was removed then dried (MgSO4), filtered and evaporated to form the crude aldehyde. The residue was then dissolved in dry dichloromethane (100 ml) followed by addition of N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochloride (5.72 g), N,N-diisopropylethylamine (3.17 mL) and NaBH(OAc)3 (9.76 g) and the reaction was stirred under argon for 18 h. 1M NaOH (50 mL) was added followed by vigorous stirring and the dichloromethane layer was extracted. The organic layer was dried (MgSO4), filtered and evaporated. Purification by chromatography (EtOAc neat) afforded the title compound (2.10 g) as a white foam LCMS M/z(+) 471, 473 (M+H+).

Workup

  1. customthe DCM layer was removed
  2. dry with materialthen dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto form the crude aldehyde
  6. stirringthe reaction was stirred under argon for 18 h
  7. stirringby vigorous stirring
  8. extractionthe dichloromethane layer was extracted
  9. dry with materialThe organic layer was dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customPurification by chromatography (EtOAc neat)

Sources & evidence

ORD record
ord-1cab6420822c4fff99eabe89fd507904
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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