Tetrahydrofuran → HCID 71257313, compound

HRID 710183Notes

Reaction equation

HRID 710183 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[O:13][C:14]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([S:27]([CH2:30][C:31](OCC)=O)(=[O:29])=[O:28])[CH2:23][CH2:22]3)=[CH:17][C:15]=2[N:16]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1C[O:45][CH2:44]C1>>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[O:13][C:14]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([S:27]([CH2:30][CH2:31][CH2:44][OH:45])(=[O:28])=[O:29])[CH2:23][CH2:22]3)=[CH:17][C:15]=2[N:16]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 71257634HCID 71257634, compound

Product 1

HCID 71257313HCID 71257313, compound

Procedure

Example 61 (0.2 g, 0.41 mmol) was dissolved in DCM and added TEA (0.33 g, 3.3 mmol). This mixture was stirred at rt for 30 mins. After 30 mins reaction mixture cooled to 0° C. and added ethyl 3-(chlorosulfonyl)propanoate (245 mg, 1.2 mmol). This reaction continued for 30 mins at rt. Work up (H2O/DCM) followed by column purification on combiflash using a gradient mixture of EtOAc and Petether (65:35) as eluent afforded ethyl 2-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl)benzo[d]oxazol-5-yl]piperidin-1-ylsulfonyl}acetate. Ethyl 2-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl)benzo[d]oxazol-5-yl]piperidin-1-ylsulfonyl}acetate (100 mg, 0.19 mmol) was dissolved in THF (5 ml) and added Lithiumaluminium hydride (14 mg, 0.37 mmol) at 0° C. This mixture was stirred at same temperature for 90 mins. After completion of the reaction, reaction mass quenched with 1N HCl (7 ml). Work up (DCM/H2O) followed by purification on combiflash using a gradient mixture of EtOAc and Petether (65:35) as eluent afforded the titled compound (120 mg) as an off-white solid. M.P.: 204-206° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 8.47 (t, J 8.03, 1H), 8.06 (dd, J 1.6, 10.1, 1H), 7.97 (dd, J 1.6, 8.2, 1H), 7.82-7.75 (m, 2H), 7.43 (dd, J 1.5, 8.6, 1H), 4.66 (t, J 5.3, 1H), 3.74 (d, J 12.1, 2H), 3.50 (q, J 6.1, 2H), 3.38 (s, 3H), 3.12-3.06 (m, 2H), 2.98-2.80 (m, 3H), 1.96-1.90 (m, 2H), 1.88-1.81 (m, 2H), 1.79-1.69 (m, 2H).

Workup

  1. customAfter completion of the reaction, reaction mass
  2. customquenched with 1N HCl (7 ml)
  3. customfollowed by purification on combiflash
  4. additiona gradient mixture of EtOAc and Petether (65:35) as eluent

Sources & evidence

ORD record
ord-975d01c0c5824dafbd84d11cbdbfbe9f
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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