Ether hydrochloride → HCID 71257133, compound

HRID 710176Notes

Reaction equation

HRID 710176 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]=[C:19]([CH:21]3[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]3)[CH:18]=[CH:17][C:15]=2[N:16]=1.O(CC)CC.[ClH:39]>C1COCC1>[ClH:39].[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:9])=[O:10])[CH:5]=[CH:4][C:3]=1[C:12]1[O:13][C:14]2[CH:20]=[C:19]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:15]=2[N:16]=1

Participants

4

Reactant 2

HCID 10953452Ether hydrochlorideHCID 71257317HCID 71257317, compound

Product 1

HCID 71257133HCID 71257133, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-6-yl}piperidine-1-carboxylate (270 mg, 5.7 mmol) dissolved in THF (5 ml) and added Et2O.HCl (10 ml). Reaction mixture stirred at rt for 3 h. Ether removed on rotavapour to obtain crude. Crude was triturated with ether to obtain 2-[2-fluoro-4-(methylsulfonyl)phenyl]-6-(piperidin-4-yl)-benzo[d]oxazole hydrochloride (225 mg). 2-[2-fluoro-4-(methylsulfonyl)phenyl]-6-(piperidin-4-yl)-benzo[d]oxazole hydrochloride (70 mg, 0.17 mmol) was dissolved in DCM (5 ml) and added TEA (0.11 ml, 0.85 mmol). This mixture stirred at rt for 30 mins and added isopropylchloro formate in toluene (42 mg, 0.34 mmol). After 30 mins reaction mixture quenched with water and extracted with DCM. DCM removed on rotavapour to obtain the crude. Crude was purified by combiflash using EtOAC and Petether (1:3) as eluent to afford the titled compound (30 mg) as a white solid. M.P.: 170.3-174.3° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.47-8.44 (m, 1H), 7.90-7.83 (m, 2H), 7.78 (d, J 8.3, 1H), 7.49 (s, 1H), 7.28 (dd. J 1.5, 8.3, 1H), 4.96 (septet, J 6.2, 1H), 4.40-4.28 (m, 2H), 3.13 (s, 3H), 2.92-2.80 (m, 3H), 1.96-1.88 (m, 2H), 1.75-1.62 (m, 2H), 1.28 (d, J 6.2, 6H).

Workup

  1. customReaction mixture
  2. customEther removed on rotavapour
  3. customto obtain crude
  4. customCrude was triturated with ether

Sources & evidence

ORD record
ord-700f913c372b4ead9bd6db825f510f1d
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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