Acetyl chloride → HCID 10867425, compound

HRID 887909Notes

Reaction equation

HRID 887909 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.).

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-a0f32ea2a27e4123a356021a6ba34a7e
Source dataset
uspto-grants-2012_08
Patent number
US08247432B2

Reaction notes

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