4-Phenylcyclohexanone → HCID 49763571, compound

HRID 1893225Notes

Reaction equation

HRID 1893225 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.OC(C(F)(F)F)=O.[NH:21]1[CH2:24][CH:23]([NH:25][C:26]([CH2:28][NH:29][C:30](=[O:41])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=2)=[O:27])[CH2:22]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([N:21]3[CH2:24][CH:23]([NH:25][C:26]([CH2:28][NH:29][C:30](=[O:41])[C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:38])[F:39])[CH:32]=4)=[O:27])[CH2:22]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 786054-PhenylcyclohexanoneHCID 5049666Sodium triacetoxyborohydrideHCID 86646678HCID 86646678, compound

Product 1

HCID 49763571HCID 49763571, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-phenyl-cyclohexanone (Aldrich, 1.5 g, 8.62 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide TFA salt (as prepared in the previous step, 3.89 g, 12.9 mmol) in DCM (20 mL) was treated with TEA (6 mL, 43 mmol) for 10 min followed by NaBH(OAc)3 (Aldrich, 3.65 g, 17.2 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 a chloroform/IPA “cocktail” (˜3:1, v/v). The combined organic layers were 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 the two title compounds as white solids.

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 a chloroform/IPA “cocktail” (˜3:1
  4. dry with materialThe combined organic layers were 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 the two title compounds as white solids

Sources & evidence

ORD record
ord-b33e184be415416ab32c3477acd29bee
Source dataset
uspto-grants-2013_08
Patent number
US08513229B2

Reaction notes

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