Triphenylphosphine → ((3S*,4R*)-1-benzyl-4-{[isopropyl-(2-nitro-benzenesulfonyl)-amino]-methyl}-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester

HRID 1158482Notes

Reaction equation

HRID 1158482 reaction equation
[C:1]([O:5][C:6](=[O:26])[N:7]([CH2:11][C@H:12]1[C@@H:16]([CH2:17]O)[CH2:15][N:14]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:13]1)[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH:27]([NH:30][S:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N+:40]([O-:42])=[O:41])(=[O:33])=[O:32])([CH3:29])[CH3:28].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.CCOCC.CCCCCC>[C:1]([O:5][C:6](=[O:26])[N:7]([CH2:11][C@H:12]1[C@@H:16]([CH2:17][N:30]([CH:27]([CH3:29])[CH3:28])[S:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[N+:40]([O-:42])=[O:41])(=[O:32])=[O:33])[CH2:15][N:14]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:13]1)[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 4154456N-isopropyl-2-nitrobenzenesulfonamideHCID 68616191((3S*,4R*)-1-Benzyl-4-hydroxymethyl-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester

Product 1

HCID 68616510((3S*,4R*)-1-benzyl-4-{[isopropyl-(2-nitro-benzenesulfonyl)-amino]-methyl}-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21584099Diethylether hexaneSolvent

Procedure

To a solution of ((3S*,4R*)-1-benzyl-4-hydroxymethyl-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester (0.60 g, 1.66 mmol), N-isopropyl-2-nitro-benzenesulfonamide (0.49 g, 1.99 mmol), and PPh3 (0.52 g, 1.99 mmol) in toluene (15 mL), is added dropwise diisopropyl azodicarboxylate (0.39 mL, 1.99 mmol) at 0° C. under a nitrogen atmosphere. The solution is stirred for 1 h at room temperature, and then heated at 65° C. for 1 h. The reaction mixture is concentrated. The crude material is used purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 3:7) to give the crude product. To the solid product is added a mixture of Et2O/hexane (1:1) and the resulting suspension is filtered. The solid is washed with Et2O/hexane (1:1) solution, and then the combined filtrate is concentrated to give a titled product. TLC, Rf (AcOEt)=0.61. MS (LC-MS): 589.3 [M+H]+; tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 6.39 min.

Workup

  1. temperatureheated at 65° C. for 1 h
  2. concentrationThe reaction mixture is concentrated
  3. customThe crude material is used purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 3:7)
  4. customto give the crude product
  5. additionTo the solid product is added
  6. filtrationthe resulting suspension is filtered
  7. washThe solid is washed with Et2O/hexane (1:1) solution
  8. concentrationthe combined filtrate is concentrated

Sources & evidence

ORD record
ord-a806a800d7a247298cb94078a1627a46
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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