Allyl chloroformate → prop-2-en-1-yl 7-(2-methyl-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473842Notes

Reaction equation

HRID 473842 reaction equation
Cl.Cl.[CH3:3][C:4]1[NH:8][C:7]2[CH:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]4[O:22][CH2:21][CH2:20][NH:19][CH2:18][C:17]=4[CH:23]=3)[CH:11]=[CH:12][C:6]=2[N:5]=1.CCN(C(C)C)C(C)C.Cl[C:34]([O:36][CH2:37][CH:38]=[CH2:39])=[O:35]>ClCCl>[CH3:3][C:4]1[NH:8][C:7]2[CH:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]4[O:22][CH2:21][CH2:20][N:19]([C:34]([O:36][CH2:37][CH:38]=[CH2:39])=[O:35])[CH2:18][C:17]=4[CH:23]=3)[CH:11]=[CH:12][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 18052Allyl chloroformate2×HCID 81531Diisopropylethylamine2×HCID 668202277-(2-methyl-1H-benzimidazol-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine dihydrochloride

Product 1

HCID 67515387prop-2-en-1-yl 7-(2-methyl-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

7-(2-methyl-1H-benzimidazol-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine dihydrochloride (6.95 g, 19.73 mmol) was suspended in dichloromethane (100 mL) and cooled to 0° C. To the resulting mixture was added DIPEA (19 mL, 109 mmol) followed by allyl chloroformate (4.6 mL, 43.4 mmol) and stirring was continued at 0° C. for 30 minutes then warmed to room temperature. The reaction mixture was then charged with additional DIPEA (3.4 mL) and allyl chloroformate (1 mL) then stirred an additional 30 minutes at room temperature. The resulting solution was then concentrated and the residue azeotroped once from methanol (100 mL). The residue was then taken back into methanol (100 mL) followed by portionwise addition of 2 M aqueous sodium hydroxide (20 mL) and the mixture was allowed to stir for 1 h at room temperature. The solution was then concentrated and the residue partitioned with chloroform and dilute brine. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated to give prop-2-en-1-yl 7-(2-methyl-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate as an amorphous residue which was carried forward directly into step 6.

Workup

  1. temperaturethen warmed to room temperature
  2. stirringthen stirred an additional 30 minutes at room temperature
  3. concentrationThe resulting solution was then concentrated
  4. customthe residue azeotroped once from methanol (100 mL)
  5. additionfollowed by portionwise addition of 2 M aqueous sodium hydroxide (20 mL)
  6. stirringto stir for 1 h at room temperature
  7. concentrationThe solution was then concentrated
  8. customthe residue partitioned with chloroform and dilute brine
  9. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-084b2e2ed1a74a5fba59809ad45fc960
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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