Acetyl chloride → HCID 10867425, compound

HRID 551387Notes

Reaction equation

HRID 551387 reaction equation
O[C:2]1([C:12]([NH2:14])=[O:13])[CH:10](O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C(N(CC)CC)C.[C:22](Cl)(=[O:24])[CH3:23]>ClC(Cl)Cl>[C:22]([N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10][C@H:2]1[C:12]([NH2:14])=[O:13])(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 6367Acetyl chloride4×HCID 8471Triethylamine4×HCID 67151914HCID 67151914, compound

Product 1

HCID 10867425HCID 10867425, compoundYield 76.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

2,3-Dihydroxy-1H-indole-2-carboxamide (0.030 mol) was suspended in trichloromethane (400 ml). The mixture was cooled to 0° C. Triethylamine (0.045 mol) was added. Acetyl chloride (0.045 mol) was added over 2 minutes. After 30 minutes, TLC showed the reaction was incomplete. While the flask was still cool, more Triethylamine (6.26 ml) was added, followed 15 minutes later with more acetyl chloride (3.21 ml). TLC showed the reaction was still incomplete. The reaction was continued to allow to stir, cooled to 0° C., and more triethylamine (6.26 ml) was added. Over 2 minutes, more acetyl chloride (3.21 ml) was added neat. TLC showed 80% completion after 60 minutes, and no progress after 30 more minutes. A third portion of acetyl chloride and triethylamine was added. After an additional 15 minutes, ice cold water (200 ml) was added. The mixture was stirred for 10 minutes, filtered, and rinsed with water (3×100 ml) and trichloromethane (2×75 ml). The sample was allowed to dry overnight, yielding 4.71 g of (S)-1-acetyl-2,3-dihydro-1H-indole-2-carboxamide (intermediate 1, mp. >260° C.). b) Intermediate (1) (0.02022 mol) was suspended in DCM (175 ml). The mixture was cooled to 0° C. Triethylamine (0.06066 mol) was added neat. Trichloroacetyl chloride (0.03033 mol) in DCM (20 ml) was added dropwise over 20 minutes. After 2 hours, ice water (200 ml) was added, the phases separated and the organic phase reextracted with 3 N HCl and then with a saturated aqueous NaHCO3 solution. The organic phase was dried, filtered, and stripped to leave 4.61 g brown solid. The solid was triturated with ice cold diethylether (30 ml), filtered, and rinsed with ice cold diethylether (twice), yielding 3.12 g (83%) of (S)-1-acetyl-2,3-dihydro-1H-indole-2-carbonitrile (intermediate 2, mp. 134-135° C.). c) Intermediate (2) (0.0151 mol) was suspended in diethylether (200 ml). Ethanol (0.0214 mol) was added, and the mixture was cooled to 0° C. HCl (gas) was bubbled in for 45 minutes. The mixture was removed from the ice bath and stirred. After 20 minutes, a residue collected on the wall sides. The walls were scratched, and a white solid precipitated out. After 1 hour the sample was filtered, rinsed with diethylether, air dried quickly, yielding 3.99 g of (S)-ethyl 1-acetyl-2,3-dihydro-1H-indole-2-carboximidate monohydrochloride (intermediate 3). In analogy, ethyl 1-acetyl-2,3-dihydro-1H-indole-2-carboximidate monohydrochloride (intermediate 6) was prepared starting from 1-acetyl-2,3-dihydro-1H-indole-2-carbonitrile.

Workup

  1. temperatureWhile the flask was still cool
  2. temperaturecooled to 0° C.
  3. waitOver 2 minutes
  4. customafter 60 minutes
  5. waitAfter an additional 15 minutes
  6. stirringThe mixture was stirred for 10 minutes
  7. filtrationfiltered
  8. washrinsed with water (3×100 ml) and trichloromethane (2×75 ml)
  9. customto dry overnight

Sources & evidence

ORD record
ord-ec1c2a0dc13c411cad9d7a62de682423
Source dataset
uspto-grants-2011_05
Patent number
US07947713B2

Reaction notes

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