Formaldehyde → (1-Methylazetidin-3-yl)methyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate

HRID 2201688Notes

Reaction equation

HRID 2201688 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]=1[NH:15][C:16](=[O:23])[O:17][CH2:18][CH:19]1[CH2:22][NH:21][CH2:20]1)([O-:3])=[O:2].[CH2:24](Cl)Cl.C=O.C([BH3-])#N.[Na+]>CC#N>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]=1[NH:15][C:16](=[O:23])[O:17][CH2:18][CH:19]1[CH2:20][N:21]([CH3:24])[CH2:22]1)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 71007325Azetidin-3-ylmethyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate

Product 1

HCID 71007324(1-Methylazetidin-3-yl)methyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamateYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of azetidin-3-ylmethyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate (0.09 g, 0.26 mmol, 1.0 eq.) in CH3CN:CH2Cl2 was added aq. formaldehyde (0.77 mmol, 3.0 eq.). The reaction mixture was stirred at room temperature for 30 min then cooled to 0° C. Sodium cyanoborohydride (0.03 g, 0.46 mmol, 1.8 eq.) was added slowly. The reaction was quenched with an aqueous saturated solution of sodium bicarbonate. The product was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 5% MeOH/CH2Cl2) to obtain (1-methylazetidin-3-yl)methyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate (0.07 g, 75% yield).

Workup

  1. temperaturethen cooled to 0° C
  2. customThe reaction was quenched with an aqueous saturated solution of sodium bicarbonate
  3. extractionThe product was extracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-17bfeab9e9a94fd3918239fdbfa160c0
Source dataset
uspto-grants-2016_06
Patent number
US09365498B2

Reaction notes

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