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

HRID 2095573Notes

Reaction equation

HRID 2095573 reaction equation
C[O:2][C:3](=O)[C@@H:4]([N:18]1[CH2:23][CH2:22][N:21]([C:24](=[O:38])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[C:28]([Cl:37])[CH:27]=2)[C@@H:20]([CH3:39])[C:19]1=[O:40])[CH2:5][CH2:6][C:7]([N:9]1[CH2:16][CH2:15][C:12]2([CH2:14][CH2:13]2)[C@H:11]([OH:17])[CH2:10]1)=[O:8].[Li+].[BH4-].CO.CC(C)=O>C1COCC1.C1CCCCC1.[OH-].[Na+]>[Cl:37][C:28]1[CH:27]=[C:26]([NH:25][C:24]([N:21]2[CH2:22][CH2:23][N:18]([C@H:4]([CH2:3][OH:2])[CH2:5][CH2:6][C:7]([N:9]3[CH2:16][CH2:15][C:12]4([CH2:13][CH2:14]4)[C@H:11]([OH:17])[CH2:10]3)=[O:8])[C:19](=[O:40])[C@@H:20]2[CH3:39])=[O:38])[CH:31]=[CH:30][C:29]=1[O:32][C:33]([F:35])([F:36])[F:34]

Participants

8

Reactant 4

HCID 180AcetoneHCID 887MethanolHCID 4148881Lithium borohydrideHCID 58232194(S)-2-[(S)-4-(3-Chloro-4-trifluoromethoxy-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-5-oxo-pentanoic acid methyl ester

Product 1

HCID 58232125(S)-4-[(S)-4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid (3-chloro-4-trifluoromethoxy-phenyl)-amideYield 88%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 0.200 g (0.34 mmol) of (S)-2-[(S)-4-(3-chloro-4-trifluoromethoxy-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-5-oxo-pentanoic acid methyl ester (example 54) in 1.0 ml of THF was treated with 0.17 ml (0.34 mmol) of LiBH4 (2 M in THF) and 0.027 ml (0.68 mmol) of MeOH (with cooling bath at RT). The reaction was stirred for 2 h at RT, cooled to 0° C. and stopped with 0.1 ml of acetone. The reaction was diluted with 0.3 ml of cyclohexane, 0.9 ml of aqueous 2 N NaOH were added and after 30 min extracted with EtOAc (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated to give after flash silica gel column (dichloromethane/MeOH 98:2 to 9:1) 0.172 g (88%) of the titled compound as white foam. MS: 577.20 (MH+, Cl).

Workup

  1. temperaturecooled to 0° C.
  2. additionwere added and after 30 min
  3. extractionextracted with EtOAc (3×)
  4. washThe organic phases were washed with aqueous 10% NaCl
  5. dry with materialdried (Na2SO4)
  6. customevaporated

Sources & evidence

ORD record
ord-0ec6c06450554cc3a588063e4aba13a4
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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