Water → HCID 86757839, compound

HRID 277140Notes

Reaction equation

HRID 277140 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[N:11]2[CH2:14][CH:13]([NH:15][CH2:16][C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=3)[CH2:12]2)=[CH:6][CH:5]=1.Cl[C:33]([O:35][CH3:36])=[O:34].O>O1CCCC1>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([CH:10]([C:7]2[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=2)[N:11]2[CH2:12][CH:13]([N:15]([CH2:16][C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=3)[C:33](=[O:34])[O:35][CH3:36])[CH2:14]2)=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 10296513HCID 10296513, compound

Product 1

HCID 86757839HCID 86757839, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

24.4 mg of a 75% dispersion of sodium hydride in mineral oil are added, at room temperature under an argon atmosphere, to a solution of 330 mg of {1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(3,5-difluorobenzyl)amine in 25 cm3 of tetrahydrofuran. The mixture is stirred at room temperature for 1 hour before adding thereto 59 mm3 of methyl chloroformate, and then the stirring is maintained for 18 hours under the same conditions. The reaction mixture is supplemented with 0.3 cm3 of distilled water and the tetrahydrofuran is expelled in a rotary evaporator. The residue obtained is extracted with dichloromethane, the organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is purified by flash chromatography on silica gel [eluent: dichloromethane/methanol (97.5/2.5 by volume)]. 328 mg of methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3,5-difluorobenzyl)carbamate are obtained in the form of a colorless oil [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 2.97 (mt: 2H); 3.39 (mt: 2H); 3.71 (s: 3H); 4.24 (broad s: 1H); 4.45 (unresolved complex: 1H); 4.57 (s: 2H); from 6.65 to 6.80 (mt: 3H); from 7.15 to 7.30 (mt: 8H)].

Workup

  1. additionbefore adding
  2. customthe tetrahydrofuran is expelled in a rotary evaporator
  3. customThe residue obtained
  4. extractionis extracted with dichloromethane
  5. dry with materialthe organic phase is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue obtained
  9. customis purified by flash chromatography on silica gel [eluent: dichloromethane/methanol (97.5/2.5 by volume)]

Sources & evidence

ORD record
ord-0de8c5c5b3cc4b4dace7f6dc94fd3355
Source dataset
uspto-grants-2002_03
Patent number
US06355631B1

Reaction notes

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