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Diisopropylethylamine → Tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide

HRID 68581
Notes
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Reaction equation

HRID 68581 reaction equation
[O:1]1[CH2:5][CH2:4][CH:3]([C:6]([OH:8])=O)[CH2:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:51][C:52]1[O:53][C:54]([C:59]2[CH2:63][C:62]([C:68]3[CH:73]=[C:72]([Cl:74])[C:71]([Cl:75])=[C:70]([Cl:76])[CH:69]=3)([C:64]([F:67])([F:66])[F:65])[O:61][N:60]=2)=[CH:55][C:56]=1[CH2:57][NH2:58]>ClCCl>[CH3:51][C:52]1[O:53][C:54]([C:59]2[CH2:63][C:62]([C:68]3[CH:73]=[C:72]([Cl:74])[C:71]([Cl:75])=[C:70]([Cl:76])[CH:69]=3)([C:64]([F:66])([F:65])[F:67])[O:61][N:60]=2)=[CH:55][C:56]=1[CH2:57][NH:58][C:6]([CH:3]1[CH2:4][CH2:5][O:1][CH2:2]1)=[O:8]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 4661317(R)-Tetrahydro-3-furoic acidHCID 86706655C-{2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-yl}-methylamine

Product 1

HCID 86706656
Tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide
Yield 76.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tetrahydro-furan-3-carboxylic acid (81 mg), PyBOP (268 mg) and DIPEA (0.244 ml) are added to a solution of C-{2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-yl}-methylamine (200 mg) in dichloromethane (4 ml). After 24 hours at room temperature, the reaction is quenched with water. The reaction mixture is extracted three times with dichloromethane. The combined organic phases are washed with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide (189 mg, compound 2.3 in Table 2) as a white foam. MS (HPLC/MS): 525 (MH+). Retention time: 1.97 min.

Workup

  1. customthe reaction is quenched with water
  2. extractionThe reaction mixture is extracted three times with dichloromethane
  3. washThe combined organic phases are washed with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-4162567a08bb4382b1be2cae6394aba4
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08822466B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes