Hydrochloric Acid → Ethyl 4,5,6,7-Tetrahydroisoindole-1-carboxylate

HRID 1434811

Reaction equation

HRID 1434811 reaction equation
N12[CH2:11][CH2:10][CH2:9][N:8]=[C:7]1[CH2:6][CH2:5][CH2:4][CH2:3]C2.[N+](C1CCCCC=1)([O-])=O.[CH2:21]([O:23][C:24](=[O:28])C[N+]#[C-])[CH3:22].Cl>CC(O)C.C1COCC1.CCOC(C)=O>[CH2:21]([O:23][C:24]([C:7]1[NH:8][CH:9]=[C:10]2[C:6]=1[CH2:5][CH2:4][CH2:3][CH2:11]2)=[O:28])[CH3:22]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 757131-NitrocyclohexeneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 533707Ethyl isocyanoacetate

Product 1

HCID 10035498Ethyl 4,5,6,7-Tetrahydroisoindole-1-carboxylate

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,8-Diazabicyclo[5.4.0]-undec-7-ene (6.2 mL, 41.5 mmol) in 2-propanol (45 mL) was added by addition funnel over ˜25 minutes to a stirring solution of 1-nitrocyclohexene (5.0441 g, 39.67 mmol) and ethylisocyanoacetate (4.3340 g, 37.16 mmol) in THF (45 mL). The reaction was judged complete after stirring overnight at room temperature. 2N HCl (˜100 mL) and EtOAc (˜50 mL) were added. The organic layer was removed, then washed with H2O, 5% NaHCO3, and H2O. The crude product was dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 100% CH2Cl2) to obtain 171 contaminated with a minor impurity. Attempts to recrystallize from hexanes were unsuccessful at removing the impurity, so the product was carried on to the next step with no further purification. 1H (CDCl3, 400 MHz): δ 9.01 (1H, broad s), 6.64 (1H, s), 4.31 (3H, q, J=7.2 Hz), 2.82 (2H, t, J=5.6 Hz), 2.55 (2H, t, J=5.6 Hz), 1.80-1.68 (4H, m), 1.36 (3H, t, J=7.2 Hz) ppm. 13C (CD3OD, 100 MHz): 6161.71, 128.06 and 127.84, 121.98 and 121.96, 118.74 and 118.55, 118.03 and 117.71, 59.62, 23.41 and 23.39, 23.36 and 23.33, 23.16 and 23.13, 21.88 and 21.86, 14.48 ppm. DEPT (CD3OD, 100 MHz): CH3 carbons: 14.48; CH2 carbons: 59.62, 23.41 and 23.39, 23.36 and 23.33, 23.16 and 23.13, 21.88 and 21.86; CH carbons: 118.74 and 118.55 ppm. HPLC: 10.689 min.

Workup

  1. customThe organic layer was removed
  2. washwashed with H2O, 5% NaHCO3, and H2O
  3. dry with materialThe crude product was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (Combiflash column, 100% CH2Cl2)

Sources & evidence

ORD record
ord-fe780ddeef8e44949416a03a61b491f9
Source dataset
uspto-grants-2009_11
Patent number
US07615572B2

Linked notes

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