4-Fluorobenzenesulfonyl chloride → (R)-Methyl 3-(4-fluorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193281Notes

Reaction equation

HRID 1193281 reaction equation
CCN(C(C)C)C(C)C.Cl.[CH3:11][O:12][C:13]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[CH2:20][CH2:19][C@H:18]2[NH2:24])=[O:14].[F:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>ClCCl>[F:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:24][C@H:18]2[C:17]3[C:21](=[CH:22][CH:23]=[C:15]([C:13]([O:12][CH3:11])=[O:14])[CH:16]=3)[CH2:20][CH2:19]2)(=[O:34])=[O:33])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 95884-Fluorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66700566(R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate hydrochloride

Product 1

HCID 66805309(R)-Methyl 3-(4-fluorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIPEA (447 μl, 2.634 mmol, 3 eq) was added at 0° C. to a solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-01) (0.878 mmol, 1 eq) in dichloromethane (10 ml). A solution of 4-fluorobenzene-1-sulfonyl chloride (170 mg, 0.878 mmol, 1 eq) dissolved in dichloromethane (6 ml) was added dropwise and the mixture was stirred for 16 h at RT. After monitoring by thin-layer chromatography. the reaction solution was concentrated under reduced pressure and the residue was taken up in ethyl acetate, washed with 10% ammonium chloride solution, sodium hydrogen carbonate solution and sat. NaCl solution (in each case 1x), dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 1:5). Yield: 88%

Workup

  1. additionwas added dropwise
  2. concentrationthe reaction solution was concentrated under reduced pressure
  3. washwashed with 10% ammonium chloride solution, sodium hydrogen carbonate solution and sat. NaCl solution (in each case 1x),
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 1:5)

Sources & evidence

ORD record
ord-95f7c3dff682482aa445a89c46cad10e
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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