Triphenylphosphine → tert-Butyl 3-[(4-{[(5-chloro-2-thienyl)carbonyl]amino}-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzylcarbamate

HRID 585509Notes

Reaction equation

HRID 585509 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[NH:25][C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1.O[CH2:34][C:35]1[CH:36]=[C:37]([CH:47]=[CH:48][CH:49]=1)[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[Cl:13][C:14]1[S:18][C:17]([C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24](=[O:32])[N:25]([CH2:34][C:35]2[CH:36]=[C:37]([CH:47]=[CH:48][CH:49]=2)[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:43])[CH3:44])[C:26]3=[O:31])=[O:20])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2794814tert-Butyl 3-(hydroxymethyl)benzylcarbamateHCID 41357405-Chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)thiophene-2-carboxamide

Product 1

HCID 22337050tert-Butyl 3-[(4-{[(5-chloro-2-thienyl)carbonyl]amino}-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2.41 ml (15.4 mmol) of diethyl azodicarboxylate (DEAD) are added dropwise to a mixture, cooled with water, of 3.37 g (11 mmol) of 5-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide, 3.26 g (13.8 mmol) of tert-butyl 3-(hydroxymethyl)benzylcarbamate and 4.04 g (15.4 mmol) of triphenylphosphine in 60 ml of absolute THF. The reaction mixture is stirred vigorously at room temperature for 90 min and then concentrated to a volume of about 30 ml. 300 ml of ether are added to the solid and the mixture is filtered. Another crystallization of the mother liquor yields a second batch. The product is dried under high vacuum. Alternatively, the product can be purified by column chromatography on silica gel (dichloromethane/methanol mixture or cyclohexane/ethyl acetate mixture). Yield: 4.79 g (82.8% of theory);

Workup

  1. concentrationconcentrated to a volume of about 30 ml
  2. addition300 ml of ether are added to the solid
  3. filtrationthe mixture is filtered
  4. customAnother crystallization of the mother liquor
  5. customyields a second batch
  6. customThe product is dried under high vacuum
  7. customAlternatively, the product can be purified by column chromatography on silica gel (dichloromethane/methanol mixture or cyclohexane/ethyl acetate mixture)

Sources & evidence

ORD record
ord-929abc5177de4fe7bea66f2f0ee313ee
Source dataset
uspto-grants-2005_08
Patent number
US06933295B2

Reaction notes

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