Cesium carbonate → Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate

HRID 1626412Notes

Reaction equation

HRID 1626412 reaction equation
I[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.[Cl:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][C:38]=1[OH:39])[O:35][CH2:34][CH2:33][CH:32]2[C:40]([O:42][CH2:43][CH3:44])=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[Cu]Cl>[C:9]([O:8][C:6]([C:5]1[CH:13]=[CH:14][C:2]([O:39][C:38]2[CH:37]=[C:36]3[C:31]([CH:32]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:33][CH2:34][O:35]3)=[CH:30][C:29]=2[Cl:28])=[CH:3][CH:4]=1)=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 11130493Tert-butyl 4-iodobenzoateHCID 53393319Ethyl-6-chloro-7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate

Product 1

HCID 67080248Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylateYield 38%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl 4-iodobenzoate (25.9 g, 85.2 mmol) and 2,2,6,6-tetramethyl-3,5-heptanedione (7.01 mL, 34.1 mmol) were diluted with NMP (70 mL) and bubbled with Argon for 20 minutes. Copper (I) chloride (16.9 g, 170 mmol), ethyl 6-chloro-7-hydroxychroman-4-carboxylate (24.0 g, 93.7 mmol) and cesium carbonate (55.5 g, 170 mmol) were combined and added to the reaction using a small funnel which was rinsed with NMP (30 mL). The reaction was purged for an additional 10 minutes and then heated to 100° C. and stirred for 5 hours under Argon. The reaction was cooled and loaded directly onto a silica plug (2 kg) and eluted with 10% ethyl acetate/hexanes to yield 10 g of crude product. The crude material was purified by silica gel column chromatography, eluting with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes to provide the desired product (14 g, 32.3 mmol, 38.0% yield) as a viscous oil.

Workup

  1. custombubbled with Argon for 20 minutes
  2. additionadded to the reaction
  3. washwas rinsed with NMP (30 mL)
  4. customThe reaction was purged for an additional 10 minutes
  5. temperatureThe reaction was cooled
  6. washeluted with 10% ethyl acetate/hexanes
  7. customto yield 10 g of crude product
  8. customThe crude material was purified by silica gel column chromatography
  9. washeluting with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-bbe6c7ed4cba427da2f5230bae84f62f
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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