1-Chloroethyl chloroformate → HCID 66710170, compound

HRID 1469350Notes

Reaction equation

HRID 1469350 reaction equation
C([N:14]1[CH2:17][CH:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:31]C(OC(Cl)C)=O>ClCCl>[ClH:31].[C:22]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:23]=[CH:24][C:19]([O:18][CH:16]2[CH2:17][NH:14][CH2:15]2)=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformate2×HCID 18379631HCID 18379631, compound

Product 1

HCID 66710170HCID 66710170, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Benzhydryl-3-(biphenyl-4-yloxy)azetidine (15.40 g, 39.34 mmol) was dissolved in dichloromethane (400 mL), stirred, and cooled in an ice-water bath. 1-Chloroethyl chloroformate (8.49 mL, 11.25 g, 78.69 mmol) was added in 1 mL portions over 10 minutes, and the mixture stirred for a further 30 minutes at 0° C., then at rt for 25.5 hours. Further 1-chloroethyl chloroformate (4.25 mL, 5.63 g, 39.35 mmol) was added and the mixture stirred for 3 days. The solvents were evaporated in vacuo and methanol (300 mL) added to the resulting white solid. The mixture was heated gently to dissolve, and then allowed to cool whilst stirring vigorously, whereupon a white precipitate formed. After a further 2 hours stirring at room temperature, the solids where collected by filtration to give the amine (7.41 g, 72%) as a white solid; mp>195° C.; LCMS retention time 1.64 mins, m/z 226.1 [M+H]+; 1H nmr (400 MHz; DMSO-d6) δ 9.26 (br s, 2H), 7.64-7.60, (m, 4H), 7.47-7.41 (m, 2H), 7.33 (ft, 1H, J=7.3 and 1.2 Hz), 6.96 (d, 2H, J=8.8 Hz), 5.13 (tt, 1H, J=6.8 and 4.8 Hz), 4:46 (dd, 2H, J=12.4 and 6.8 Hz) and 4.01 (dd, 2H, J=12.4 and 4.8 Hz).

Workup

  1. temperaturecooled in an ice-water bath
  2. stirringthe mixture stirred for a further 30 minutes at 0° C.
  3. stirringthe mixture stirred for 3 days
  4. customThe solvents were evaporated in vacuo and methanol (300 mL)
  5. additionadded to the resulting white solid
  6. temperatureThe mixture was heated gently
  7. dissolutionto dissolve
  8. temperatureto cool
  9. stirringwhilst stirring vigorously, whereupon a white precipitate
  10. customformed
  11. stirringAfter a further 2 hours stirring at room temperature
  12. filtrationthe solids where collected by filtration

Sources & evidence

ORD record
ord-978b960087ee45eabb6a5ff45739d2c5
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Reaction notes

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