2-Chlorobenzoyl chloride → HCID 66798901, compound

HRID 1193271Notes

Reaction equation

HRID 1193271 reaction equation
Cl.[NH2:2][C@H:3]1[C:11]2[C:6](=[CH:7][C:8]([C:13]([O:15][CH3:16])=[O:14])=[C:9]([F:12])[CH:10]=2)[CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.[Cl:26][C:27]1[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=1[C:29](Cl)=[O:30]>ClCCl>[Cl:26][C:27]1[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=1[C:29]([NH:2][C@H:3]1[C:11]2[C:6](=[CH:7][C:8]([C:13]([O:15][CH3:16])=[O:14])=[C:9]([F:12])[CH:10]=2)[CH2:5][CH2:4]1)=[O:30]

Participants

5

Reactant 3

HCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 66798889HCID 66798889, compound

Product 1

HCID 66798901HCID 66798901, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-Methyl 1-amino-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate hydrochloride (A-05) (0.23 g, 1.18 mmol, 1 eq) was dissolved in dichloromethane and DIPEA (2.5 eq), under nitrogen, and 2-chlorobenzoic acid chloride (0.15 ml, 1.18 mmol, 1 eq) was added at 0° C. The reaction mixture was stirred for 2 h at RT. Then the reaction mixture was concentrated and the residue was taken up in ethyl acetate, washed with 10% ammonium chloride solution and with sat. NaCl solution, dried over magnesium sulfate and concentrated. The crude product was purified by column chromatography (silica gel, cyclohexane:ethyl acetate 3:1) and the desired product (R)-methyl 1-(2-chlorobenzamido)-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate (B-28) was thus obtained. Yield: 83%.

Workup

  1. concentrationThen the reaction mixture was concentrated
  2. washwashed with 10% ammonium chloride solution and with sat. NaCl solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (silica gel, cyclohexane:ethyl acetate 3:1)

Sources & evidence

ORD record
ord-840524a47370421e908f08bb64716cdc
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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