Phosgene → HCID 9815014, compound

HRID 895334Notes

Reaction equation

HRID 895334 reaction equation
[CH2:1]([SH:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[C:10](Cl)(Cl)=O.[NH2:14][C:15]1[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].ClC1C=CSC=1C(OCCCCCCCC)=O>C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CCOCC>[CH2:1]([S:9][C:10]1[O:18][C:17](=[O:19])[C:16]2[CH:20]=[CH:21][C:22]([CH3:24])=[CH:23][C:15]=2[N:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]

Participants

9

Reactant 4

HCID 6371PhosgeneHCID 81441-OctanethiolHCID 753164-Methylanthranilic acidHCID 69133002HCID 69133002, compound

Product 1

HCID 9815014HCID 9815014, compoundYield 14.1%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Octanethiol (0.71 ml, 4.1 mmol) was dissolved in THF (10 ml). To this solution was added a solution of phosgene (20% in PhMe, 3.5 ml, 7.4 mmol). After 2.5 h the reaction vessel was purged with nitrogen to remove excess phosgene and hydrogen chloride, the vented gas being passed through a scrubber containing dilute aqueous sodium hydroxide. The crude octyl chlorothiolformate solution was used directly. 2-Amino-4-methylbenzoic acid (151 mg, 1 mmol) was dissolved in pyridine (0.5 ml) and DCM (5 ml). To this was added one quarter of the crude octyl chlorothiolformate solution (1 mmol, assuming 100% from the first step). After 24 h, the reaction was diluted with ether and washed with 1M aqueous HCl and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexane gradient) to give a solid which was triturated with acetonitrile to afford the title compound (43 mg, 14%): δH (400 MHz, CDCl3) 0.82 (3H, t, J 6.7, Me), 1.21-1.24 (8H, m, 4×CH2), 1.37-1.41 (2H, m, SCH2CH2CH2), 1.68-1.72 (2H, m, SCH2CH2), 2.40 (3H, s, ArMe), 3.08 (2H, t, J 7.4, SCH2), 7.16 (1H, d, J 8.0, ArH), 7.19 (1H, d, J 1.4, ArH), 7.93 (1H, d, J 8.0, ArH); m/z (ES+) 306 (MH+).

Workup

  1. customAfter 2.5 h the reaction vessel was purged with nitrogen
  2. customto remove excess phosgene and hydrogen chloride
  3. additioncontaining dilute aqueous sodium hydroxide
  4. washwashed with 1M aqueous HCl and brine
  5. dry with materialThe organic phase was dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (EtOAc/hexane gradient)
  8. customto give a solid which
  9. customwas triturated with acetonitrile

Sources & evidence

ORD record
ord-e23e2db5ceb749f7af7eb27e2d611dbf
Source dataset
uspto-grants-2005_07
Patent number
US06916808B2

Reaction notes

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