Triethylamine → n-(2-{[(9s)-7-(4-Hydroxy-4-phenylcyclohexyl)-1-oxa-7-azaspiro[4.4]non-9-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

HRID 1025690Notes

Reaction equation

HRID 1025690 reaction equation
[O:1]1[C:5]2([C@@H:9]([NH:10][C:11](=[O:26])[CH2:12][NH:13][C:14](=[O:25])[C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[CH2:8][NH:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[OH:27][C:28]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CCN(CC)CC>C1COCC1>[OH:27][C:28]1([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:29][CH2:30][CH:31]([N:7]2[CH2:8][C@H:9]([NH:10][C:11](=[O:26])[CH2:12][NH:13][C:14](=[O:25])[C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)[C:5]3([O:1][CH2:2][CH2:3][CH2:4]3)[CH2:6]2)[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5837414-Hydroxy-4-phenylcyclohexan-1-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59556036n-{2-[(9s)-1-Oxa-7-azaspiro[4.4]non-9-ylamino]-2-oxoethyl}-3-(trifluoromethyl)benzamide

Product 1

HCID 10098936n-(2-{[(9s)-7-(4-Hydroxy-4-phenylcyclohexyl)-1-oxa-7-azaspiro[4.4]non-9-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the amine of step H (90 mg, 0.243 mmol) and 4-hydroxy-4-phenyl-cyclohexanone (43 mg, 0.226 mmol) in THF (5 mL) was added sodium triacetoxyborohydride (129 mg, 0.61 mmol) followed by Et3N (0.29 ml, 2 mmol). The mixture was stirred at room temperature overnight. Solvent was removed under vacuum. The residue was taken up in EtOAc/NaHCO3 aqueous solution. The two phases were separated and the water layer was extracted with EtOAc twice. The combined organic phase was dried (Na2SO4) and concentrated. Purification by prep-HPLC provided two isomers. MS: 546.4 (M+1)+.

Workup

  1. customSolvent was removed under vacuum
  2. customThe two phases were separated
  3. extractionthe water layer was extracted with EtOAc twice
  4. dry with materialThe combined organic phase was dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification
  7. customby prep-HPLC provided two isomers

Sources & evidence

ORD record
ord-16ed4c0be0dc49f1a3ca076b447bda65
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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