Sodium Hydroxide → 4-((2-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)morpholino)methyl)benzoic acid

HRID 529383Notes

Reaction equation

HRID 529383 reaction equation
FC(F)(F)C([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.[CH:24]([C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[CH:28][CH:27]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.CO>[C:9]1([C@@H:7]2[CH2:8][C@H:6]2[NH:5][CH2:15][CH:16]2[CH2:17][N:18]([CH2:24][C:26]3[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=3)[CH2:19][CH2:20][O:21]2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 15294Methyl 4-FormylbenzoateHCID 5049666Sodium triacetoxyborohydrideHCID 867082742,2,2-Trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide

Product 1

HCID 665715394-((2-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)morpholino)methyl)benzoic acidYield 72.5%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide (100 mg, 0.305 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 4-formylbenzoate (60.0 mg, 0.365 mmol) and sodium triacetoxyborohydride (97 mg, 0.457 mmol), and the mixture was stirred at room temperature for 18 h. The reaction was then quenched with water (5 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was dissolved into methanol (3.00 mL) and sodium hydroxide (6M, 0.5 mL, 3.00 mmol) was added. The mixture was stirred at room temperature for 18 h and purified using reverse-phase HPLC. The fractions containing the product were combined, treated with 1N HCl and concentrated. The residue was dried under vacuum to give 81 mg of product (HCl salt) as white solid. MS: (M+H)+=367.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.36 (m, 1H), 1.50 (br. s., 1H), 2.93 (br. s., 2H), 3.10 (br. s., 2H), 3.35 (br. s., 2H), 4.05 (br. s., 2H), 4.36 (br. s., 2H), 7.10-7.39 (m, 5H), 7.74 (br. s., 2H) 8.01 (m, 2H).

Workup

  1. customThe reaction was then quenched with water (5 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. additionwas added
  6. stirringThe mixture was stirred at room temperature for 18 h
  7. custompurified
  8. additionThe fractions containing the product
  9. additiontreated with 1N HCl
  10. concentrationconcentrated
  11. customThe residue was dried under vacuum

Sources & evidence

ORD record
ord-252611d798964330aaa54197a8047d5d
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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