Water → HCID 13324761, compound

HRID 371498Notes

Reaction equation

HRID 371498 reaction equation
Cl.[N:2]1([C:11]2[CH:12]=[C:13]([CH2:17][NH:18][CH3:19])[CH:14]=[CH:15][CH:16]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29].O>C(Cl)Cl>[CH2:31]([O:30][C:28]([N:18]([CH3:19])[CH2:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([N:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)[CH:12]=1)=[O:29])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 13324742HCID 13324742, compound

Product 1

HCID 13324761HCID 13324761, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

An ice cold rapidly stirred solution of 7.73 g (28.18 mmole) of 3-(1-indolinyl)-N-methyl benzenemethanamine hydrochloride of Example 8b in 150 ml CH2Cl2 was treated dropwise with a solution of 9.9 ml (70.45 mmole, 2.5 equivalents) of triethylamine in 10 ml CH2Cl2. After stirring for three minutes, a solution of 4.0 ml (42.27 mmole, 1.5 equivalents) ethyl chloroformate in 10 ml CH2Cl2 was added dropwise. At the end of the addition the reaction mixture was permitted to warm to room temperature, stirred for 1 hour and stand about 64 hours. Water (200 ml) was added and the organic layer was separated and washed with 2N HCl (200 ml), water (300 ml), brine (300 ml), dried (Na2SO4), and concentrated to give 7.64 g (87.3%) of crude product. Chromatography on silica gel (85 g) using ether-methylene chloride afforded 6.73 g (76.9% overall) of an oil of N-ethoxycarbonyl-3-(1-indolinyl)-N-methylbenzenemethanamine, bp>240° C./0.1 mm.

Workup

  1. additionAt the end of the addition the reaction mixture
  2. stirringstirred for 1 hour
  3. waitstand about 64 hours
  4. customthe organic layer was separated
  5. washwashed with 2N HCl (200 ml), water (300 ml), brine (300 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give 7.64 g (87.3%) of crude product

Sources & evidence

ORD record
ord-fbbae45a312a45a7a13e2410db82ec9d
Source dataset
uspto-grants-1985_07
Patent number
US04532333

Reaction notes

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