Methanol → (NE,S)-2-methyl-N-[[2-[4-(trifluoromethyl)phenyl]pyrimidin-5-yl]methylidene]propane-2-sulfinamide

HRID 1427500Notes

Reaction equation

HRID 1427500 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[CH3:19][C:20]([S@@:23]([NH2:25])=[O:24])([CH3:22])[CH3:21].CO.C([O-])(O)=O.[Na+]>ClCCl.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12](/[CH:15]=[N:25]/[S@:23]([C:20]([CH3:22])([CH3:21])[CH3:19])=[O:24])=[CH:11][N:10]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 219363042-(4-Trifluoromethyl-phenyl)-pyrimidine-5-carbaldehyde

Product 1

HCID 140585864(NE,S)-2-methyl-N-[[2-[4-(trifluoromethyl)phenyl]pyrimidin-5-yl]methylidene]propane-2-sulfinamideYield 99.3%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carbaldehyde (35.25 g, 138.9 mmol) was suspended in anhydrous dichloromethane (470 mL) in a 3-necked 1 L flask with overhead stirrer, condenser and internal temperature. (S)-(−)-2-methyl-2-propanesulfinamide (17.13 g, 141.3 mmol) was added followed by titanium(IV) ethoxide (37.3 mL, 178 mmol). This gave a yellow solution which was heated to reflux for 3 h. The heating was discontinued and the reaction placed in an ice bath. When the internal temperature was −10° C., anhydrous methanol (246 mL) was added followed by sat. aq. NaHCO3 (71 mL). Solid crashed out which was stirred for 2 h. The solids were filtered off with a Buchner funnel using ethyl acetate to aid in transfer. Several portions of ethyl acetate were used to rinse the solid. The solid was added back into the 3-necked flask and mechanically stirred for 20 min with ethyl acetate. This was refiltered. This process was repeated to remove most of the product. The filtrate was dried over Na2SO4 and concentrated in vacuo to give (S)-2-methyl-propane-2-sulfinic acid 1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-meth-(E)-ylideneamide (49.00 g, 99%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 9.25 (s, 2H) 8.70 (s, 1H) 8.66 (d, J=8.2 Hz, 2H) 7.79 (d, J=8.2 Hz, 2H) 1.31 (s, 9H); MS (M+1): 356.1.

Workup

  1. customThis gave a yellow solution which
  2. temperaturewas heated
  3. temperatureto reflux for 3 h
  4. customthe reaction placed in an ice bath
  5. customwas −10° C.
  6. filtrationThe solids were filtered off with a Buchner funnel
  7. washto rinse the solid
  8. additionThe solid was added back into the 3-necked flask
  9. stirringmechanically stirred for 20 min with ethyl acetate
  10. customto remove most of the product
  11. dry with materialThe filtrate was dried over Na2SO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6226850983ec4f2aae1ec3b7870fee61
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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