Hydrochloric Acid → Methyl 6-[(isopropoxycarbonyl)amino]indane-5-carboxylate

HRID 604617Notes

Reaction equation

HRID 604617 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12].NC1C=CC2CCCC=2C=1C(OC)=O.N1C=CC=CC=1.Cl[C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37].Cl>C(Cl)Cl>[CH:39]([O:38][C:36]([NH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12])=[O:37])([CH3:41])[CH3:40]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 59379136methyl 6-amino-2,3-dihydro-1H-indene-5-carboxylateHCID 67057733Methyl 5-aminoindane-4-carboxylate

Product 1

HCID 59003158Methyl 6-[(isopropoxycarbonyl)amino]indane-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of a mixture of methyl 6-aminoindane-5-carboxylate and methyl 5-aminoindane-4-carboxylate (760 mg, 3.98 mmol), and pyridine (805 uL, 9.95 mmol) in CH2Cl2 (8 mL) at 0° C. under N2 was added isopropyl chloroformate (1 M in toluene) (3.98 mL, 3.98 mmol). The resulting mixture was stirred at room temperature for 16 h. 1M HCl was added to the reaction mixture and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, hexanes/EtOAc) to afford methyl 6-[(isopropoxycarbonyl)amino]indane-5-carboxylate. LCMS calc.=300.1; found=299.9 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H); 8.34 (s, 1H); 7.86 (s, 1H); 5.06-5.00 (m, 1H); 3.92 (s, 3H); 2.96 (t, J=7.5 Hz, 2H); 2.88 (t, J=7.4 Hz, 2H); 2.13-2.07 (m, 2H); 1.33 (d, J=6.2 Hz, 6H). Methyl 5-[(isopropoxycarbonyl)amino]indane-4-carboxylate was isolated as a by-product. LCMS calc.=300.1; found=299.9 (M+Na)+. 1H NMR (500 MHz, CDCl3) a 10.07 (s, 1H); 8.21 (d, J=8.4 Hz, 1H); 7.36 (d, J=8.4 Hz, 1H); 5.06-5.00 (m, 1H); 3.93 (s, 3H); 3.19 (t, J=7.5 Hz, 2H); 2.89 (t, J=7.5 Hz, 2H); 2.08-2.02 (m, 2H); 1.32 (d, J=6.2 Hz, 6H).

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with CH2Cl2 (2×)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (Si, hexanes/EtOAc)

Sources & evidence

ORD record
ord-e46b960c9f88460bbed32ed96bb00d44
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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