Sodium triacetoxyborohydride → N-({1-[4-Hydroxy-4-(6-methoxy-pyridin-3-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2096142Notes

Reaction equation

HRID 2096142 reaction equation
[OH:1][C:2]1([C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.Cl.[NH:18]1[CH2:21][CH:20]([NH:22][C:23]([CH2:25][NH:26][C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=2)=[O:24])[CH2:19]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[OH:1][C:2]1([C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[CH2:7][CH2:6][CH:5]([N:18]2[CH2:21][CH:20]([NH:22][C:23]([CH2:25][NH:26][C:27](=[O:38])[C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:35])[F:36])[CH:29]=3)=[O:24])[CH2:19]2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 529879954-Hydroxy-4-(6-methoxypyridin-3-YL)cyclohexanoneHCID 66750350N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt

Product 1

HCID 46241509N-({1-[4-Hydroxy-4-(6-methoxy-pyridin-3-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Hydroxy-4-(6-methoxy-pyridin-3-yl)-cyclohexanone, as prepared in Step B of this example, (300 mg, 1.36 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt, as prepared in Step D of this example, (460 mg, 1.36 mmol) in DCM (5 mL) were treated with TEA (1 mL, 7.12 mmol) for 10 min followed by NaBH(OAc)3 (860 mg, 4.07 mmol) for another 4 hours at room temperature. The reaction was quenched with saturated sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford two title compounds as white solids: a less polar isomer, and a more polar isomer.

Workup

  1. customThe reaction was quenched with saturated sodium bicarbonate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1
  4. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas then purified by a CombiFlash® system
  9. customto afford two title compounds as white solids

Sources & evidence

ORD record
ord-94ed8471fd9a4c489595ab98577bbc56
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

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