Oxalyl chloride → 2-[(5,6,7,8-Tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047693Notes

Reaction equation

HRID 1047693 reaction equation
[C:1]1([C:11]([OH:13])=O)[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[CH2:20]([O:22][C:23]([C:25]1([NH2:34])[CH2:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26]1)=[O:24])[CH3:21].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:20]([O:22][C:23]([C:25]1([NH:34][C:11]([C:1]2[C:10]3[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=3[CH:4]=[CH:3][CH:2]=2)=[O:13])[CH2:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26]1)=[O:24])[CH3:21]

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 2396045,6,7,8-Tetrahydro-1-naphthalenecarboxylic acidHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 593141592-[(5,6,7,8-Tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 59.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 5,6,7,8-tetrahydro-naphthalene-1-carboxylic acid (500 mg, 2.84 mmol) in DCM (10 mL) is added oxalyl chloride (0.50 mL, 5.68 mmol) dropwise. The resulting solution is stirred at RT for 2 h. After the removal of DCM and excess oxalyl chloride, the residue, 2-amino-indan-2-carboxylic acid ethyl ester (583 mg, 2.84 mmol) and DIPEA (1.88 mL, 11.3 mmol) are dissolved in DCM (20 mL). The resulting solution is stirred overnight. The reaction solution is diluted with DCM (30 mL) and washed with water (1×5 mL) and brine (2×5 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (120 g silica gel, gradient elution: 0%-20% EtOAc in heptane) to give the pure product (37) as white solid (610 mg, 59%).

Workup

  1. customAfter the removal of DCM and excess oxalyl chloride
  2. stirringThe resulting solution is stirred overnight
  3. washwashed with water (1×5 mL) and brine (2×5 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography (120 g silica gel, gradient elution: 0%-20% EtOAc in heptane)

Sources & evidence

ORD record
ord-0d1454b282c44fb18e18a30d01d7592a
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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