Hydrochloric Acid → 3-Chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (2-methoxy-5-pyridin-4-ylbenzyl)-(4-methyl-aminocyclohexyl)amide

HRID 2389731Notes

Reaction equation

HRID 2389731 reaction equation
C(OC(=O)[NH:7]C1CCC(NCC2C=C(C3C=NC=CC=3)C=CC=2OC)CC1)(C)(C)C.C(OC(=O)N[CH2:38][CH:39]1[CH2:44][CH2:43][CH:42]([N:45]([C:61]([C:63]2[S:64][C:65]3[C:72]([F:73])=[CH:71][CH:70]=[C:69]([F:74])[C:66]=3[C:67]=2[Cl:68])=[O:62])[CH2:46][C:47]2[CH:52]=[C:51]([C:53]3[CH:58]=[CH:57][N:56]=[CH:55][CH:54]=3)[CH:50]=[CH:49][C:48]=2[O:59][CH3:60])[CH2:41][CH2:40]1)(C)(C)C.Cl>CCO>[CH3:60][O:59][C:48]1[CH:49]=[CH:50][C:51]([C:53]2[CH:58]=[CH:57][N:56]=[CH:55][CH:54]=2)=[CH:52][C:47]=1[CH2:46][N:45]([C:42]1([NH2:7])[CH2:41][CH2:40][CH:39]([CH3:38])[CH2:44][CH2:43]1)[C:61]([C:63]1[S:64][C:65]2[C:72]([F:73])=[CH:71][CH:70]=[C:69]([F:74])[C:66]=2[C:67]=1[Cl:68])=[O:62]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 59766919[4-(2-Methoxy-5-pyridin-3-yl-benzylamino)-cyclohexyl]-carbamic acid tert-butyl esterHCID 86618979{4-[(3-Chloro-4,7-difluorobenzothiophene-2-carbonyl)-(2-methoxy-5-pyridin-4-ylbenzyl)amino]cyclohexyl}methylcarbamic acid tert-butyl ester

Product 1

HCID 866189803-Chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (2-methoxy-5-pyridin-4-ylbenzyl)-(4-methyl-aminocyclohexyl)amide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
5 °C

Procedure

To a 3 L 3-neck RB flask with a mechanical stirrer, addition funnel, temperature probe and N2 inlet is added {4-[(3-chloro-4,7-difluorobenzothiophene-2-carbonyl)-(2-methoxy-5-pyridin-4-ylbenzyl)amino]cyclohexyl}methylcarbamic acid tert-butyl ester P6 (54.92 g, 83.70 mmol) and EtOH (1.5 L). The resulting beige slurry is cooled to 5° C. and concentrated HCl (800 mL) is added over 1 h. The cold bath is removed and the solution is stirred for 4.5 h at room temperature. The reaction mixture is concentrated by removing 1.5 L solvent in vacuo and H2O (500 mL) is added. The mixture is extracted with CH2Cl2 (2×350 mL). The aqueous layer is cooled to 2° C. and 50% NaOH (300 mL) is added to pH=13. The mixture is extracted with CH2Cl2 (3×600 mL) and the combined organic layers are washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo to give 3-chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (2-methoxy-5-pyridin-4-ylbenzyl)-(4-methyl-aminocyclohexyl)amide n (46.5 g, 99%) as a tan foam.

Workup

  1. additionTo a 3 L 3-neck RB flask with a mechanical stirrer, addition funnel
  2. customThe cold bath is removed
  3. concentrationThe reaction mixture is concentrated
  4. customby removing 1.5 L solvent in vacuo and H2O (500 mL)
  5. additionis added
  6. extractionThe mixture is extracted with CH2Cl2 (2×350 mL)
  7. temperatureThe aqueous layer is cooled to 2° C.
  8. addition50% NaOH (300 mL) is added to pH=13
  9. extractionThe mixture is extracted with CH2Cl2 (3×600 mL)
  10. washthe combined organic layers are washed with brine
  11. dry with materialdried over anhydrous Na2SO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b86b5f7becdb4ed59bc653c1de2eedf4
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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