Benzyl chloroformate → HCID 118116472, compound

HRID 1754846Notes

Reaction equation

HRID 1754846 reaction equation
[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:4]([C:15]2[C:20]3[S:21][C:22]([CH:24]([CH3:26])[CH3:25])=[N:23][C:19]=3[CH2:18][CH2:17][N:16]=2)[CH:3]=1.[BH4-].[Na+].CCN(C(C)C)C(C)C.Cl[C:39]([O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:40]>CCO.C(Cl)Cl>[CH2:42]([O:41][C:39]([N:16]1[CH2:17][CH2:18][C:19]2[N:23]=[C:22]([CH:24]([CH3:25])[CH3:26])[S:21][C:20]=2[CH:15]1[C:4]1[CH:3]=[C:2]([Cl:1])[CH:14]=[CH:13][C:5]=1[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:40])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

7

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 90022223HCID 90022223, compound

Product 1

HCID 118116472HCID 118116472, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of ethyl 2-(4-chloro-2-(2-isopropyl-6,7-dihydrothiazolo[5,4-c]pyridin-4-yl)phenoxy)acetate (33 mg, 84 μmol, 1.0 eq.) in EtOH (5 mL), NaBH4 (3.5 mg, 92 μmol, 1.1 eq.) was added. The cooling bath was removed and the yellow solution was stirred at r.t. for 2 hours. The reaction mixture was poured in water (15 mL). The mixture was extracted with DCM (2×20 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. To an-ice cooled solution of the residue and DIPEA (43 μL, 252 μmol, 3.0 eq.) in DCM (5 mL), benzyl chloroformate (14 μL, 92 μmol, 1.1 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the solution was stirred at r.t. for 1 hour. The reaction was quenched with 1M aq. citric acid soln. (5 mL). The layers were separated. The aq. phase was extracted with DCM (3×5 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to afford the title compound as a yellow oil.

Workup

  1. additionwas added
  2. customThe cooling bath was removed
  3. additionThe reaction mixture was poured in water (15 mL)
  4. extractionThe mixture was extracted with DCM (2×20 mL)
  5. dry with materialphases were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. additionUpon completion of the addition
  8. customthe cooling bath was removed
  9. stirringthe solution was stirred at r.t. for 1 hour
  10. customThe reaction was quenched with 1M aq. citric acid soln
  11. customThe layers were separated
  12. extractionThe aq. phase was extracted with DCM (3×5 mL)
  13. dry with materialphases were dried over MgSO4
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by prep
  16. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Sources & evidence

ORD record
ord-a13075be2ed1480e9becdb6fad289347
Source dataset
uspto-grants-2015_10
Patent number
US09169270B2

Reaction notes

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