4-Methylmorpholine → (S)-4-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid (4-trifluoromethoxy-phenyl)-amide

HRID 2095561Notes

Reaction equation

HRID 2095561 reaction equation
[OH:1][C@@H:2]1[CH2:9][N:8]([C:10](=[O:22])[CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][NH:17][C@@H:16]([CH3:20])[C:15]2=[O:21])[CH2:7][CH2:6][C:3]21[CH2:5][CH2:4]2.CN1CCOCC1.[N:30]([C:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]([F:43])([F:42])[F:41])=[CH:35][CH:34]=1)=[C:31]=[O:32]>ClCCl>[F:41][C:40]([F:42])([F:43])[O:39][C:36]1[CH:35]=[CH:34][C:33]([NH:30][C:31]([N:17]2[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][C:10]([N:8]3[CH2:7][CH2:6][C:3]4([CH2:5][CH2:4]4)[C@H:2]([OH:1])[CH2:9]3)=[O:22])[C:15](=[O:21])[C@@H:16]2[CH3:20])=[O:32])=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 92298p-(Trifluoromethoxy)phenyl isocyanate4×HCID 67074162HCID 67074162, compound2×

Product 1

HCID 58232205(S)-4-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid (4-trifluoromethoxy-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.050 g (0.16 mmol) of (S)-1-[4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-3-methyl-piperazin-2-one (intermediate 13) and 0.053 ml (0.48 mmol) of 4-methylmorpholine in 1 ml of dichloromethane was treated at RT with 0.033 g (0.16 mmol) of 1-isocyanato-4-trifluoromethoxy-benzene (intermediate 14) in 1 ml of dichloromethane. After 1 h again 0.005 g of 0.033 g (0.16 mmol) of 1-isocyanato-4-trifluoromethoxy-benzene (intermediate 14) were added and after 30 min the reaction was extracted with aqueous 10% KHSO4/EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3, 10% NaCl and dried over Na2SO4 to yield, after precipitation with dichloromethane/pentane, 0.077 g (93%) of the titled compound as white amorphous solid. MS: 513.23 (MH+).

Workup

  1. extractionwas extracted with aqueous 10% KHSO4/EtOAc (3×)
  2. washThe organic phases were washed with aqueous saturated NaHCO3, 10% NaCl
  3. dry with materialdried over Na2SO4
  4. customto yield
  5. customafter precipitation with dichloromethane/pentane, 0.077 g (93%) of the titled compound as white amorphous solid

Sources & evidence

ORD record
ord-9120f59679c24361886bba4074d84f4b
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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