Diazomethane → HCID 57659762, compound

HRID 1011597Notes

Reaction equation

HRID 1011597 reaction equation
[CH3:1][N:2]([N:9]=O)C(N[N+]([O-])=O)=N.[OH-].[K+].[Si:13]([O:20][C@H:21]1[CH2:25][N:24]([S:26]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[C@H:23]([CH:39]=[CH2:40])[CH2:22]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[N+](=[CH2:43])=[N-].C([O-])(O)=O.[Na+]>CCOCC.[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl>[N+:2](=[CH2:1])=[N-:9].[Si:13]([O:20][C@H:21]1[CH2:25][N:24]([S:26]([C:29]2[CH:30]=[CH:31][C:32]([C:35]([F:36])([F:37])[F:38])=[CH:33][CH:34]=2)(=[O:28])=[O:27])[C@H:23]([CH:39]2[CH2:43][CH2:40]2)[CH2:22]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

11

Reactant 5

HCID 9550DiazomethaneHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 57659777HCID 57659777, compoundHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 2

HCID 9550DiazomethaneHCID 57659762HCID 57659762, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

An ethereal solution of diazomethane was prepared by adding 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) (2.84 g, 19.3 mmol) to a biphasic solution (10 ml 40% KOH/5 ml ether) and stirring at 0° C. for 5 minutes. The biphasic solution was cooled to −78° C. to freeze the aqueous layer. The diazomethane solution was decanted into a vial containing a solution of (6) (0.841 g, 1.93 mmol) in 5 ml of ether. Palladium (II) acetate (43.3 mg, 0.193 mmol) was added and the reaction was stirred for 30 min. This procedure of adding diazomethane solution followed by palladium catalyst was repeated 2 more times to produce a greater yield. Dichloromethane (10 ml) was added followed by sat. NaHCO3 (5 ml). The catalyst was filtered off and the organic layer was isolated and dried over sodium sulfate. The organic layer was concentrated in vacuo and purified via column chromatography using ethyl acetate/hexane gradients to yield (2S,4R)-4-(tert-butyldimethylsilyloxy)-2-cyclopropyl-1-(4-(trifluoromethyl)phenylsulfonyl)pyrrolidine (10) (0.520 g, 60%) as a clear oil. This was a mixture of (R) (64%) and (S) (36%) isomers. MS m/z 449.1 (M+H)+; retention time=7.069 min ((R)-isomer) and 7.292 ((S) isomer); method [10].

Workup

  1. temperatureThe biphasic solution was cooled to −78° C.
  2. customThe diazomethane solution was decanted into
  3. stirringthe reaction was stirred for 30 min
  4. customto produce
  5. customa greater yield
  6. filtrationThe catalyst was filtered off
  7. customthe organic layer was isolated
  8. dry with materialdried over sodium sulfate
  9. concentrationThe organic layer was concentrated in vacuo
  10. custompurified via column chromatography

Sources & evidence

ORD record
ord-549172a512194776bb55a91cb13b1703
Source dataset
uspto-grants-2011_07
Patent number
US07977368B2

Reaction notes

Loading…