Diisopropylethylamine → 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide

HRID 1783873Notes

Reaction equation

HRID 1783873 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:21][C@@H:22]([CH:25]([CH3:27])[CH3:26])[CH2:23][OH:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCCCCC.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([NH:21][C@H:22]([CH2:23][OH:24])[CH:25]([CH3:27])[CH3:26])=[O:11])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 640993L-ValinolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684826142-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid

Product 1

HCID 684813832-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramideYield 41%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid (2.00 g, 7.11 mmol, 1.0 eq.), 2-(S)-Amino-3-methyl-butan-1-ol (1.59 g, 7.33 mmol, 1.03 eq.) and HATU (2.41 g, 7.33 mmol, 1.03 mmol) were dissolved in CH2Cl2 and stirred at room temperature. Diisopropylethylamine (3.9 mL, 21.98 mmol, 3.1 eq.) was added via syringe and the reaction is monitored by LC/MS. Upon completion, there reaction was evaporated and is diluted with ethyl acetate (100 mL) and extracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Column chromatography (0-100%) EtOAc in hexane gradient provided 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide as a clear oil (1.06 g, 2.89 mmol, 41%). HPLC-MS calcd. for C19H27FN2O4 (M+H+) 367.2, found 367.4; TLC (1:1 hexane/EtOAc) Rf=0.15.

Workup

  1. customUpon completion, there reaction
  2. customwas evaporated
  3. additionis diluted with ethyl acetate (100 mL)
  4. extractionextracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-982f8fedc2954565b07439f8735834fd
Source dataset
uspto-grants-2009_03
Patent number
US07501408B2

Reaction notes

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