Dichloromethane → HCID 178501490, compound

HRID 1985796Notes

Reaction equation

HRID 1985796 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:8][S:9][CH2:10]C1C=CC=CN=1)[C:4]([O:6][CH3:7])=[O:5].[F:17][C:18]([F:29])([F:28])[C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=O.CC[N:32]([CH:36]([CH3:38])C)[CH:33]([CH3:35])C.Cl[CH2:40]Cl>CO.C(OCC)(=O)C.[Ti](Cl)(Cl)(Cl)Cl>[N:32]1[CH:33]=[CH:35][CH:40]=[CH:38][C:36]=1[SH:9]([CH3:10])[CH2:8][C@H:3]([NH:2][CH:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:18]([F:29])([F:28])[F:17])[C:4]([O:6][CH3:7])=[O:5]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 695642,2,2,4'-TetrafluoroacetophenoneHCID 81531DiisopropylethylamineHCID 66972784HCID 66972784, compound

Product 1

HCID 178501490HCID 178501490, compound

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalyst2×HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of methyl 2(R)-amino-3-(pyridin-2-ylmethylsulfanyl)-propionate hydrochloride (1.31 g, 5 mmol), 2,2,2-trifluoro-1-(4-fluorophenyl)ethanone (0.875 g), DIPEA (2.39 g, 18.5 mmol), in dichloromethane (20 mL) was added titanium tetrachloride (4.65 mmol) dropwise over 5 min. After stirring for 3 h at ambient temperature, additional titanium tetrachloride (0.3 mmol) was added. After an additional hour of stirring, NaCNBH4 (0.973 g, 15.5 mmol) was added in methanol (10 mL). After 1 h, the reaction mixture was diluted with ethyl acetate (200 mL) and poured onto magnesium sulfate. After filtration and concentration, the residue was purified by flash chromatography to afford methyl 3-(pyridin-2-yl-methylsulfanyl)-2(R)-[2,2,2-trifluoro-1(RS)-(4-fluorophenyl)ethylamino]-propionate (640 mg, 1.59 mmol).

Workup

  1. stirringAfter an additional hour of stirring
  2. waitAfter 1 h
  3. additionpoured onto magnesium sulfate
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d8e45f3a5d27496aa541aa94a6b9703f
Source dataset
uspto-grants-2009_06
Patent number
US07547701B2

Reaction notes

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