Hydroxylamine → 3-([1,1'-biphenyl)-4-ylsulfonyl)-N-[3-phenoxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide

HRID 1964839Notes

Reaction equation

HRID 1964839 reaction equation
S1CCNC1.NO.[C:8]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:13]=[CH:12][C:11]([S:14]([N:17]2[CH2:21][CH2:20][S:19][CH:18]2[C:22]([NH:24][CH:25]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:26][CH2:27][OH:28])=[O:23])(=[O:16])=[O:15])=[CH:10][CH:9]=1.[C:41]1(O)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:8]1([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:13]=[CH:12][C:11]([S:14]([N:17]2[CH2:21][CH2:20][S:19][CH:18]2[C:22]([NH:24][CH:25]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:26][CH2:27][O:28][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:23])(=[O:16])=[O:15])=[CH:10][CH:9]=1

Participants

8

Reactant 6

HCID 787HydroxylamineHCID 996PhenolHCID 10444ThiazolidineHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 103110413-([1,1'-biphenyl]-4-ylsulfonyl)-N-(3-hydroxy-1-phenylpropyl)-1,3-thiazolidine-2-carboxamide

Product 1

HCID 102897323-([1,1'-biphenyl)-4-ylsulfonyl)-N-[3-phenoxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamideYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Thiazolidine intermediates of general structure (XXVI), e.g., 3-([1,1′-biphenyl]-4-ylsulfonyl)-N-(3-hydroxy-1-phenylpropyl)-1,3-thiazolidine-2-carboxamide (1.0 g, 1.0 eq, 2.07 mmol) was dissolved in 20 ml dry THF under nitrogen. Phenol (252 mg, 1.5 eq, 2.69 mmol), diethylazodicarboxylate (470 mg, 1.5 eq, 2.69 mmol) and triphenyl phosphine polymer bound (1.0 g, 1.5 eq, 2.70 mmol) were then added and the reaction mixture was shaken for 12 hours at RT. Triphenyl phosphine resin was filtered off and the THF solution evaporated in vacuo. The residue was taken up in DCM and washed twice with saturated sodium carbonate solution and then water. The organic layer was dried with magnesium sulfate and concentrated in vacuo to give a crude product which was purified on silica gel using cyclohexane/ethyl acetate(8/2) as eluent, affording the desired products of general structure (XXVII), e.g., 3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[3-phenoxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide as a white oil in 40% yield and 95.5% purity by HPLC.

Workup

  1. additionwere then added
  2. filtrationTriphenyl phosphine resin was filtered off
  3. customthe THF solution evaporated in vacuo
  4. washwashed twice with saturated sodium carbonate solution
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a crude product which
  8. customwas purified on silica gel

Sources & evidence

ORD record
ord-48577732d6e64a11a819e3e1984b13e3
Source dataset
uspto-grants-2013_04
Patent number
US08415480B2

Reaction notes

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