Ethyl Acetate → 4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

HRID 1626378Notes

Reaction equation

HRID 1626378 reaction equation
C([O:5][C:6]([C:8]1[CH:30]=[CH:29][C:11]([O:12][C:13]2[CH:22]=[C:21]3[C:16]([CH:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:18][CH2:19][O:20]3)=[CH:15][C:14]=2[Cl:28])=[CH:10][CH:9]=1)=[O:7])(C)(C)C.C(OCC)(=O)C>Cl>[Cl:28][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:13]=1[O:12][C:11]1[CH:29]=[CH:30][C:8]([C:6]([OH:7])=[O:5])=[CH:9][CH:10]=1)[O:20][CH2:19][CH2:18][CH:17]2[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 67080248Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate

Product 1

HCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidYield 102.8%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate (221 g, 0.511 mol) was dissolved in hydrogen chloride in ethyl acetate (2.4 N, 1.6 L, 3.84 mol) and the resulting solution was stirred at ambient temperature for 16 hours. The solution was concentrated to give 198 g of crude 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)-benzoic acid. The crude product was recrystallized by dissolving in hot isopropyl acetate (0.5 L) and diluting with hexanes (1.1 L). After 48 hours, the crystals were collected and wash with hexanes. The resulting white solids were dried under high vacuum to give 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (169 g, 88% yield). 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J=8.9 Hz, 2H), 7.38 (s, 1H), 6.98 (d, J=8.8 Hz, 2H), 6.60 (s, 1H), 4.21-4.31 (m, 4H), 3.75 (t, J=5.4 Hz, 1H), 2.31-2.37 (m, 1H), 2.08-2.15 (m, 1H), 1.32 (t, J=7.0 Hz, 3H).

Workup

  1. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-ce4d5493e8654d2e8488dc2e845f7a74
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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