Acetyl chloride → HCID 59717857, compound

HRID 2224703Notes

Reaction equation

HRID 2224703 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:25](Cl)(=[O:27])[CH3:26].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:25](=[O:27])[CH3:26])=[CH:21][CH:22]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6367Acetyl chloride2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 59717851HCID 59717851, compound2×

Product 1

HCID 59717857HCID 59717857, compoundYield 88.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Add a solution of {2-[4-(4-Amino-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.2 g, 3.66 mmol) in dichloromethane (25 mL) dropwise to a solution of acetyl chloride (0.35 g, 4.50 mmol) in dichloromethane (125 mL) at room temperature. Upon complete addition of the amine, add triethylamine (0.74 g, 7.32 mmol) and a crystal of DMAP to the reaction and stirred at room temperature for 18 hours. Add an additional 65 uL of acetyl chloride to the reaction and stir an additional 2 hours. Pour the reaction into saturated aqueous sodium bicarbonate then extract with dichloromethane (3×100 mL). Dry the dichloromethane extracts over sodium chloride/magnesium sulfate, filter, then concentrate on a rotary evaporator to yield 1.3 g of the crude product. The crude product is purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes to yield {2-[4-(4-acetylamino-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.2 g): 1H NMR (CDCl3, 300.00 MHz): 8.00 (s, 1H), 7.49 (d, 2H, J=8.8 Hz), 7.13 (d, 2H, J=8.4 Hz), 6.98-6.89 (m, 4H), 4.69 (s, 1H), 3.37 (d, 2H, J=6.2 Hz), 2.77 (t, 2H, J=7.0 Hz), 2.18 (s, 3H), 1.46 (s, 9H).

Workup

  1. customto the reaction
  2. stirringstir an additional 2 hours
  3. additionPour
  4. extractionthen extract with dichloromethane (3×100 mL)
  5. dry with materialDry the dichloromethane
  6. filtrationfilter
  7. concentrationconcentrate on a rotary evaporator
  8. customto yield 1.3 g of the crude product
  9. customThe crude product is purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-6e19630f984d406db1acb19caa938ae4
Source dataset
uspto-grants-2008_05
Patent number
US07378448B2

Reaction notes

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