Trichloroacetyl chloride → HCID 178454073, compound

HRID 1257702Notes

Reaction equation

HRID 1257702 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([O:14][CH2:15][C:16](=O)[NH2:17])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(Cl)(Cl)C(Cl)=O>C(Cl)Cl.O>[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([O:14][CH2:15][C:16]#[N:17])[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6420Trichloroacetyl chlorideHCID 8471TriethylamineHCID 178454074HCID 178454074, compound

Product 1

HCID 178454073HCID 178454073, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of trans (4-carbamoylmethoxy-cyclohexyl)-carbamic acid tert-butyl ester (500 mg, 1.80 mmol) and triethylamine (510 μL, 3.70 mmol) in DCM (9 mL) at 0° C. was treated dropwise with a solution of 2,2,2-trichloroacetyl chloride (310 μL, 2.80 mmol) in DCM (1 mL). After the addition the mixture was stirred at ambient temperature for 45 minutes. The reaction mixture was diluted with water and the phases separated. The aqueous phase was extracted with DCM (2×) and the combined organic phases washed with a 10% citric acid solution, a saturated sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated under vacuum. Purification by column chromatography on silica gel (gradient: 0-40% ethyl acetate in cyclohexane) to afford 280 mg (60%) of trans (4-cyanomethoxy-cyclohexyl)-carbamic acid tert-butyl ester as a white solid. LCMS (Method Q, ESI): RT=3.53 min, m+H=255.0; 1H NMR (400 MHz, CDCl3) δ: 4.37 (s, 1H), 4.27 (s, 2H), 3.47 (m, 1H), 2.05 (d, 4H), 1.44 (s, 9H), 1.38 (m, 2H), 1.18 (m, 2H).

Workup

  1. additionAfter the addition the mixture
  2. customthe phases separated
  3. extractionThe aqueous phase was extracted with DCM (2×)
  4. washthe combined organic phases washed with a 10% citric acid solution
  5. dry with materiala saturated sodium bicarbonate solution and brine, dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customPurification by column chromatography on silica gel (gradient: 0-40% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-0390b3ace4dd4c4f9fb5389b5d6d3e7c
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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