Triphenylphosphine → HCID 68708074, compound

HRID 1818814Notes

Reaction equation

HRID 1818814 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[NH:10][S:9]2(=[O:18])=[O:17])=[C:4]([F:19])[CH:3]=1.O[CH2:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[C:32]([O:31][C:29](=[O:30])[NH2:26])([CH3:35])([CH3:34])[CH3:33].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]([CH2:21][CH2:22][CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[S:9]2(=[O:17])=[O:18])=[C:4]([F:19])[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineHCID 5363146Diisopropyl azodicarboxylateHCID 68708330HCID 68708330, compound

Product 1

HCID 68708074HCID 68708074, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 1-(4-chloro-2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (100 mg, 0.335 mmol), tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (147 uL, 0.67 mmol), and triphenylphosphine (176 mg, 0.67 mmol) in anhydrous tetrahydrofuran was added diisopropylazodicarboxylate (130 uL, 0.67 mmol) and the solution stirred, capped, at room temperature for 18 hr. The reaction mixture was concentrated then loaded directly onto silica gel and purified via Isco chromatography (Redisep, silica, gradient 0-35% ethyl acetate in hexane to afford 1-(4-chloro-2-fluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide carbamic acid tert-butyl ester as an orange colored wax. This material was dissolved in diethyl ether and methanol and 2N HCl in diethyl ether was added a precipitate formed. The mixture was filtered to afford impure product. This material was dissolved in DMSO and purified by Gilson RP-HPLC (YMC CombiPrep ProC18 50×20 mm I.D. column, S-5□m, 12 nm. Flow rate 20 mL/min. Gradient: 10/90 Acetonitrile/Water to 100% acetonitrile over 10 minutes then hold for three minutes at 100% acetonitrile and ramp back to 10/90 acetonitrile/water over two minutes) to give 0.089 g of 1-(4-chloro-2-fluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide as an orange solid.

Workup

  1. customcapped, at room temperature for 18 hr
  2. concentrationThe reaction mixture was concentrated
  3. custompurified via Isco chromatography (Redisep, silica, gradient 0-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-903d3d4cff674f67bcb57d52d9ca2020
Source dataset
uspto-grants-2009_10
Patent number
US07601722B2

Reaction notes

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