Ethyl 4-(3-oxopropyl)benzoate → Ethyl 4-(3-(2-((2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)acetamido)methyl)morpholino)propyl)benzoate

HRID 529381Notes

Reaction equation

HRID 529381 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]([N:5]([CH2:15][CH:16]1[O:21][CH2:20][CH2:19][NH:18][CH2:17]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:4].O=[CH:25][CH2:26][CH2:27][C:28]1[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:23][C:2]([F:22])([F:1])[C:3]([N:5]([CH2:15][CH:16]1[CH2:17][N:18]([CH2:25][CH2:26][CH2:27][C:28]2[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=2)[CH2:19][CH2:20][O:21]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:4]

Participants

5

Reactant 3

HCID 2757377Ethyl 4-(3-oxopropyl)benzoateHCID 5049666Sodium triacetoxyborohydrideHCID 867082742,2,2-Trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide

Product 1

HCID 86708275Ethyl 4-(3-(2-((2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)acetamido)methyl)morpholino)propyl)benzoate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide (150 mg, 0.457 mmol) in 1,2-dichloroethane (DCE) (3 mL) were added ethyl 4-(3-oxopropyl)benzoate (113 mg, 0.548 mmol) and sodium triacetoxyborohydride (145 mg, 0.685 mmol), and the mixture was stirred at room temperature for 18 h. The reaction was quenched with water (5 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 20 to 100% EtOAc/hexanes) to give 200 mg or product as colorless oil. MS: (M+H)+=395.2. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.34-1.46 (m, 4H), 1.56 (br. s., 1H), 1.71-1.94 (m, 3H), 2.07-2.22 (m, 1H), 2.29-2.46 (m, 2H), 2.57 (br. s., 1H), 2.67-2.78 (m, 3H), 3.12-3.22 (m, 1H), 3.53-3.69 (m, 3H), 3.75-3.94 (m, 2H), 4.29-4.43 (m, 2H), 7.07-7.46 (m, 7H), 7.89-8.04 (m, 2H).

Workup

  1. customThe reaction was quenched with water (5 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified
  6. customto give 200 mg or product as colorless oil

Sources & evidence

ORD record
ord-3fe5dc54235b4ab7abe6aba5d874cfa1
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

Loading…