9-Fluorenylmethyl chloroformate → HCID 69767535, compound

HRID 1384873Notes

Reaction equation

HRID 1384873 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:28])[O:13][CH2:12][C:11]=2[S:10][C:9]=1[NH2:29])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[C:36]([O:38][CH2:39][CH:40]1[C:52]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[C:46]2[C:41]1=[CH:42][CH:43]=[CH:44][CH:45]=2)=[O:37]>ClCCl.O>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][N:18]3[C:19](=[O:28])[C:20]4[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:26]3=[O:27])[O:13][CH2:12][C:11]=2[S:10][C:9]=1[NH:29][C:36]([O:38][CH2:39][CH:40]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:46]=2[C:47]2[C:52]1=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:37])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 22084100HCID 22084100, compound

Product 1

HCID 69767535HCID 69767535, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 2-amino-5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (4.5 g, 0.011 mole) dissolved in dichloromethane (30 ml), was added sodium bicarbonate (1.0 g, 0.011 mole) dissolved in water (16 ml). The reaction mixture was cooled to 0° C. and 9-fluorenylmethyl chloroformate (3.0 g, 0.012 mole) was added. After stirring for 5 minutes the reaction mixture was warmed to room temperature and stirred vigorously for 16 h. The organic layer was separated and washed with brine (10 ml). The aqueous phase was extracted with dichloromethane (2×20 ml) and the combined organic phases were dried (MgSO4), filtered and evaporated in vacuo to give an orange solid which was purified by flash chromatography using dichloromethane as eluent. Pure fractions were collected and evaporated in vacuo affording 5.6 g (81%) of 5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid.

Workup

  1. temperaturewas warmed to room temperature
  2. stirringstirred vigorously for 16 h
  3. customThe organic layer was separated
  4. washwashed with brine (10 ml)
  5. extractionThe aqueous phase was extracted with dichloromethane (2×20 ml)
  6. dry with materialthe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give an orange solid which
  10. customwas purified by flash chromatography
  11. customPure fractions were collected
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-b995154a76e84e5fa1bdbfa107dfd642
Source dataset
uspto-grants-2001_07
Patent number
US06262044B1

Reaction notes

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