Trifluoroacetic acid → HCID 21978406, compound

HRID 10232Notes

Reaction equation

HRID 10232 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[S:6]([CH2:9][CH:10]1[CH2:13][N:12]([C:14](OC(C)(C)C)=O)[CH2:11]1)(=[O:8])=[O:7].C(O)(C(F)(F)F)=O.[BH3-]C#N.[Na+].[S:32]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[C:34](C=O)=[N:33]1>C(Cl)Cl>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[S:6]([CH2:9][CH:10]1[CH2:11][N:12]([CH2:14][C:34]2[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[S:32][N:33]=2)[CH2:13]1)(=[O:7])=[O:8]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 1260711973437-27-1HCID 21978417HCID 21978417, compound

Product 1

HCID 21978406HCID 21978406, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 3-[(1,3-thiazol-2-ylsulfonyl)methyl]azetidine-1-carboxylate (51 mg, 0.16 mmol) was dissolved in DCM (0.5 mL) and TFA (0.5 mL) was added. The resulting mixture was stirred for 30 min. then concentrated in vacuo. The residual oil was taken up in MeOH (2 mL), then NaCNBH3 (16.2 mg, 0.26 mmol) and 1,2-benzisothiazole-3-carbaldehyde (28.6 mg, 0.18 mmol) [prepared by the method of T. Hasegawa, Y. Akiyama, T. Imai, E. Sato, Y. Yamamoto, J. Tanaka, H. Nagaso, K. Fuji, K. Murase, M. Shiiyama, WO 98/08816] were added. The mixture was stirred overnight then partitioned between 0.5 N NaOH (20 mL) and EtOAc (20 mL). The aqueous phase was washed with EtOAc (20 mL) and the organic layers were combined, washed with saturated brine (20 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified using column chromatography, on silica gel, eluting with 50–60% EtOAc in DCM to give the title compound as a colourless oil (19 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 2.96–3.06 (1H, m), 3.12 (2H, m), 3.57 (2H, t, J=7.6 Hz), 3.72 (2H, d, J=7.3 Hz), 4.04 (2H, s), 7.41–7.45 (1H, m), 7.50–7.54 (1H, m), 7.74 (1H, d, J=3.1 Hz), 7.91 (1H, d, J=8.2 Hz), 8.05 (1H, d, J=3.0 Hz), 8.10 (1H, d, J=8.1 Hz). m/z (ES+) 366 (M+H)+.

Workup

  1. concentrationthen concentrated in vacuo
  2. additionShiiyama, WO 98/08816] were added
  3. stirringThe mixture was stirred overnight
  4. customthen partitioned between 0.5 N NaOH (20 mL) and EtOAc (20 mL)
  5. washThe aqueous phase was washed with EtOAc (20 mL)
  6. washwashed with saturated brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified
  10. washon silica gel, eluting with 50–60% EtOAc in DCM

Sources & evidence

ORD record
ord-eab3cf5bbfa84edebeddc16063e41490
Source dataset
uspto-grants-2006_08
Patent number
US07094777B2

Reaction notes

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