Ammonium Chloride → 3-(2-chloro-3-fluorobenzyl)-1-((S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-hydroxypropan-2-yl)-1-methylurea

HRID 409849Notes

Reaction equation

HRID 409849 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([N:19]([CH3:32])[C:20]([NH:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1[Cl:31])=[O:21])[CH2:11][C@@H:12]1[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[O:13]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[NH4+].[Cl-]>C1COCC1>[Cl:31][C:25]1[C:26]([F:30])=[CH:27][CH:28]=[CH:29][C:24]=1[CH2:23][NH:22][C:20](=[O:21])[N:19]([C@H:10]([CH2:9][OH:8])[CH2:11][C@@H:12]1[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[O:13]1)[CH3:32]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 579477701-((S)-1-(tert-butyldimethylsilyloxy)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)propan-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea

Product 1

HCID 579475573-(2-chloro-3-fluorobenzyl)-1-((S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-hydroxypropan-2-yl)-1-methylureaYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the above crude 1-((S)-1-(tert-butyldimethylsilyloxy)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)propan-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea in THF (300 mL) was added tetrabutylammonium fluoride (10.0 mL, 1 M in THF, 10.0 mmol). The resulting solution was then stirred at RT for 1 h. The reaction mixture was added into a saturated aqueous solution of NH4Cl (350 mL) and extracted with EtOAc (2×350 mL). Combined organic layers were washed with Brine (2×400 mL) and dried over MgSO4. The solution was then concentrated. The resulting residue was purified on a silica gel column using a mixture of DCM and MeOH to give 3-(2-chloro-3-fluorobenzyl)-1-((S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-hydroxypropan-2-yl)-1-methylurea (2.3 g, 61% over two steps). LRMS (M+H+) m/z 375.1.

Workup

  1. extractionextracted with EtOAc (2×350 mL)
  2. washCombined organic layers were washed with Brine (2×400 mL)
  3. dry with materialdried over MgSO4
  4. concentrationThe solution was then concentrated
  5. customThe resulting residue was purified on a silica gel column
  6. additiona mixture of DCM and MeOH

Sources & evidence

ORD record
ord-d4516b532eb9413d9ba92d1ca775ac9e
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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