HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Diisopropylethylamine → (2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 404221
Notes
Print preview

Reaction equation

HRID 404221 reaction equation
C(N(C(C)C)C(C)C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[F:28][C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:37]1[O:41][N:40]=[C:39]([CH2:42][CH2:43][C@@:44]([CH3:52])([S:48]([CH3:51])(=[O:50])=[O:49])[C:45](O)=[O:46])[CH:38]=1.[O:53]1[CH2:58][CH2:57][CH2:56][CH2:55][CH:54]1[O:59][NH2:60]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:28][C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:37]1[O:41][N:40]=[C:39]([CH2:42][CH2:43][C@@:44]([CH3:52])([S:48]([CH3:51])(=[O:50])=[O:49])[C:45]([NH:60][O:59][CH:54]2[CH2:55][CH2:56][CH2:57][CH2:58][O:53]2)=[O:46])[CH:38]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817509(2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)butanoic acid

Product 1

HCID 86709154(2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide
Yield 102.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

N,N-Dimethy-4-aminopyridine (0.04 g, 0.3 mmol, 0.2 equiv), N-ethyl-N-isopropylpropan-2-amine (0.97 mL, 5.8 mmol, 4.5 equiv), T3P® (50% w/w solution in ethyl acetate, 3.0 mL, 4.96 mmol, 4.0 equiv), and (2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (0.46 g, 1.24 mmol, 1.0 equiv) were allowed to stir at room temperature for 30 min. A solution of O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.16 g, 1.3 mmol, 1.2 equiv) in ethyl acetate (15 mL) was added, and the reaction was allowed to stir overnight (18 h) at room temperature. Water (40 mL) was added, and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (25 g silica gel column, 0-100% gradient ethyl acetate in hexanes) to provide (2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (0.60 g, 10%). MS (LCMS) m/z 469.1 (M−1).

Workup

  1. stirringto stir overnight (18 h) at room temperature
  2. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash chromatography (25 g silica gel column, 0-100% gradient ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d7b3d66afa5349e1aa46a862afcfe44a
Source dataset
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08748466B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes