Dichloromethane → HCID 68611909, compound

HRID 2095362Notes

Reaction equation

HRID 2095362 reaction equation
C(OC([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][OH:29])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=O)(C)(C)C.C(Cl)[Cl:31]>FC(F)(F)C(O)=O.O>[ClH:31].[NH:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][OH:29])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1

Participants

5

Reactant 2

HCID 6344DichloromethaneHCID 59371507HCID 59371507, compound

Product 1

HCID 68611909HCID 68611909, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

3-[2-[5-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]ethyl]phenylmethanol is dissolved in a mixture of trifluoroacetic acid, CH2Cl2, and water. The reaction is allowed to proceed at room temperature until the starting material is no longer detected by TLC. The solvent is evaporated, and the residue is purified by preparative HPLC (for example, acetonitrile/water gradient on C18). The product-containing fraction is partially evaporated to remove CH3CN, and the product is extracted into CH2Cl2. The organic phase is dried over MgSO4 and evaporated. The residue is taken up in methanol and adsorbed on a cation exchange column. The column is first eluted with methanol to remove neutral or acidic impurities (including residual trifluoroacetic acid), then with methanolic ammonia to recover the product as free base. After evaporation, this material is dissolved in a small volume of methanol, neutralized with a small excess of hydrochloric acid, diluted with water, and lyophilized to yield the product.

Workup

  1. customto proceed at room temperature until the starting material
  2. customThe solvent is evaporated
  3. customThe product-containing fraction is partially evaporated
  4. customto remove CH3CN
  5. extractionthe product is extracted into CH2Cl2
  6. dry with materialThe organic phase is dried over MgSO4
  7. customevaporated
  8. washThe column is first eluted with methanol
  9. customto remove neutral
  10. customacidic impurities (including residual trifluoroacetic acid), then with methanolic ammonia to recover the product as free base
  11. customAfter evaporation
  12. dissolutionthis material is dissolved in a small volume of methanol
  13. additiondiluted with water
  14. customto yield the product

Sources & evidence

ORD record
ord-8cc6d1968e3844f5b06440b0c2cc1bfb
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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