Acetonitrile → {5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-carbamic acid tert-butyl ester

HRID 2045949Notes

Reaction equation

HRID 2045949 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:22]([F:25])([F:24])[F:23])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([CH:19]=O)=[C:16]([CH3:21])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:26](NC(=O)[O-])([CH3:29])([CH3:28])[CH3:27].FC(F)(F)[C:36]([OH:38])=[O:37].C([SiH](CC)CC)C.C(#[N:50])C>C(OCC)(=O)C>[C:26]([O:38][C:36](=[O:37])[NH:50][CH2:19][C:17]1[S:18][C:14]([C:11]2[CH2:10][C:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)([C:22]([F:24])([F:23])[F:25])[O:13][N:12]=2)=[CH:15][C:16]=1[CH3:21])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 21252905Tert-butylcarbamate2×HCID 866812905-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carbaldehyde

Product 1

HCID 66587403{5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carbaldehyde (Example 1, (ii) step B, 1.5 g), tert-butylcarbamate (1.32 g), trifluoroacetic acid (0.57 ml) and triethylsilane (1.81 ml) in acetonitrile (15 ml) is stirred at room temperature for 20 hours. Additional tert-butylcarbamate (1.32 g), trifluoroacetic acid (0.57 ml) and triethylsilane (1.81 ml) are added and the reaction mixture is stirred at room temperature for a further 24 hours. After diluting with ethyl acetate, the reaction mixture is quenched with a saturated solution of NaHCO3. The organic phase is separated and the aqueous phase is extracted once with ethyl acetate. The combined organic phases are extracted 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 {5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-carbamic acid tert-butyl ester (1.28 g) as a light yellow foam. MS (HPLC/MS): 509 (MH+). Retention time: 2.32 min.

Workup

  1. stirringthe reaction mixture is stirred at room temperature for a further 24 hours
  2. customthe reaction mixture is quenched with a saturated solution of NaHCO3
  3. customThe organic phase is separated
  4. extractionthe aqueous phase is extracted once with ethyl acetate
  5. extractionThe combined organic phases are extracted with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-9b331f42529246e1bb43a827edc9c6b8
Source dataset
uspto-grants-2013_11
Patent number
US08592418B2

Reaction notes

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