Diisopropylethylamine → [8-Benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73014Notes

Reaction equation

HRID 73014 reaction equation
[CH2:1]([N:8]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[O:16][C:10]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:26]([O:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][C:31]=1[CH3:39])([CH3:28])[CH3:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([N:8]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[O:16][C:10]2([CH2:15][CH2:14][N:13]([C:34]([C:33]3[CH:37]=[CH:38][C:30]([O:29][CH:26]([CH3:27])[CH3:28])=[C:31]([CH3:39])[CH:32]=3)=[O:35])[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592729354-Isopropoxy-3-methylbenzoic acidHCID 683107744-Benzyl-2-(4-chlorophenyl)-1-oxa-4,9-diazaspiro[5.5]undecane

Product 1

HCID 70872873[8-Benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanoneYield 29.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecane (100 mg, 0.28 mmol) and 4-isopropoxy-3-methyl-benzoic acid (54 mg, 0.28 mmol) in DMF (1 mL) was added DIEA (98 μL, 0.56 mmol) followed by the addition of HATU (128 mg, 0.34 mmol). The reaction mixture was stirred for 10 minutes, then quenched with water and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water (twice). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0 to 50% EtOAc/hexanes as eluent to obtain [8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (44 mg, 29%). ESI-MS m/z calc. 532.2. Found 533.3 (M+1)+; Retention time: 2.17 minutes (3 min run).

Workup

  1. customquenched with water
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was washed with water (twice)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-616c8c08190040b18a4e7bda4ebcb61d
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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