Acetic Acid → methyl[3-((2R)-2-{[(1R)-1-phenyl-ethyl]-amino}-propyl)-phenyl]-acetate

HRID 494427Notes

Reaction equation

HRID 494427 reaction equation
O=[C:2]([CH3:15])[CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:7]=[CH:8][CH:9]=1.[CH3:16][C@@H:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[C:18]1([C@H:17]([NH:24][C@H:2]([CH3:15])[CH2:3][C:4]2[CH:5]=[C:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH3:16])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6431891-Phenethylamine, (+)-HCID 5049666Sodium triacetoxyborohydrideHCID 21035403Methyl [3-(2-oxopropyl)phenyl]acetate

Product 1

HCID 46938717methyl[3-((2R)-2-{[(1R)-1-phenyl-ethyl]-amino}-propyl)-phenyl]-acetateYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl [3-(2-oxopropyl)phenyl]acetate (Preparation 90) (45.3 g, 236 mmol), (R)-α-methyl benzylamine (27.6 ml, 214 mmol), sodium triacetoxyborohydride (68.1 g, 321 mmol) and acetic acid (14.7 ml, 257 mmol) in dichloromethane (1500 ml) was stirred at room temperature for 18 hours. The reaction mixture was quenched by addition of saturated aqueous sodium bicarbonate (600 ml) and allowed to stir until effervescence ceased. The organic phase was separated and the aqueous phase extracted with further dichloromethane (2×100 ml). The combined organic extracts were washed with brine (100 ml), dried (sodium sulfate), filtered through celite and reduced in vacuo. The oil was dissolved in methanol (200 ml), treated with 1M hydrogen chloride in methanol (300 ml) and reduced in vacuo to give a 4:1 mixture of diastereomers (R,R major) as an off-white, hydrochloride salt. Two successive crystallisations (diisopropylether/methanol) gave the title compound (27.3 g) as a colourless crystalline solid.

Workup

  1. customThe reaction mixture was quenched by addition of saturated aqueous sodium bicarbonate (600 ml)
  2. customThe organic phase was separated
  3. extractionthe aqueous phase extracted with further dichloromethane (2×100 ml)
  4. washThe combined organic extracts were washed with brine (100 ml)
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered through celite
  7. dissolutionThe oil was dissolved in methanol (200 ml)
  8. additiontreated with 1M hydrogen chloride in methanol (300 ml)
  9. customto give
  10. customTwo successive crystallisations (diisopropylether/methanol)

Sources & evidence

ORD record
ord-5a7f682a7b0e49b8a9edd85a9f07ccde
Source dataset
uspto-grants-2009_05
Patent number
US07538141B2

Reaction notes

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