Acetyl chloride → HCID 178474532, compound

HRID 853127Notes

Reaction equation

HRID 853127 reaction equation
[CH2:1]([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([O:24][Si](CC)(CC)CC)([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[C:39](Cl)(=[O:41])[CH3:40].[NH4+].[Cl-]>C(Cl)Cl.CCOCC>[CH2:1]([N:8]([C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([OH:24])([C:20]([F:23])([F:21])[F:22])[C:16]([F:19])([F:17])[F:18])[CH2:11][CH2:10]1)[C:39](=[O:41])[CH3:40])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 178477573HCID 178477573, compound

Product 1

HCID 178474532HCID 178474532, compoundYield 114.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 50 mg (0.11 mmol) of trans benzyl-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-amine (example 3.1) in 1 mL of CH2Cl2 was treated with 0.1 mL of NEt3, cooled to 0° C. and treated with 0.14 mL (1.97 mmol) of acetylchloride. The mixture was stirred for 30 min and distributed between a saturated aqueous solution of NH4Cl and Et2O. The crude material obtained after drying of the combined organic phases over Na2SO4 and evaporation of the solvent was redissolved in 1 mL of THF, treated with an excess of TBAF and left to stir for 1 hr. Distribution between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases over Na2SO4, evaporation of the solvent and chromatography on silica gel with EtOAc/heptane 1:1 gave 50 mg (95%) of trans N-benzyl-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-cyclohexyl]-acetamide as a colorless viscous oil, MS: 398 (M+H)+.

Workup

  1. customThe crude material obtained
  2. dry with materialafter drying of the combined organic phases over Na2SO4 and evaporation of the solvent
  3. dissolutionwas redissolved in 1 mL of THF
  4. additiontreated with an excess of TBAF
  5. waitleft
  6. stirringto stir for 1 hr
  7. dry with materialDistribution between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases over Na2SO4, evaporation of the solvent and chromatography on silica gel with EtOAc/heptane 1:1

Sources & evidence

ORD record
ord-e2fee590b771475988e1193e6d097e83
Source dataset
uspto-grants-2007_08
Patent number
US07253282B2

Reaction notes

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