Phenol → HCID 69607065, Verbindung

HRID 965833Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 965833
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@@H:8]([CH2:11][OH:12])[O:7][C:6]=2[CH:13]=1.[C:14]1(O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@@H:8]([CH2:11][O:12][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:7][C:6]=2[CH:13]=1

Komponenten

6

Edukt 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 66879096(R)-(7-Bromo-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol

Produkt 1

HCID 69607065HCID 69607065, VerbindungAusbeute 37,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of [(2R)-7-bromo-2,3-dihydro-1,4-benzodioxin-2-yl]methanol (0.648 g, 2.64 mmol), phenol (0.248 g, 2.64 mmol), triphenylphosphine (0.692 g, 2.64 mmol) and THF (26 mL) is cooled in a 0° C. bath under N2. Diethylazodicarboxylate (0.42 ml, 2.7 mmol) is added and the mixture allowed to warm to rt overnight. The mixture is concentrated, partitioned between EtOAc and H2O, the organic layer dried (MgSO4), adsorbed onto SiO2, and chromatographed (Biotage 40S+SIM, (1:19) EtOAc:hexane). The product fractions are pooled and concentrated to afford 0.315 g (37%) of (2R)-7-bromo-2-(phenoxymethyl)-2,3-dihydro-1,4-benzodioxine as an oil. A solution of this oil (0.280 g, 0.87 mmol) and THF (30 ml) is cooled in a CO2 (s)/acetone bath under N2. To this is added a solution of tert-butyl lithium in pentane (1.7 M, 1.10 ml, 1.9 mmol). After stirring for 5 min, CO2 (g) is bubbled through the solution for an additional 10 min. The mixture is treated with MeOH/HCl and allowed to warn to rt. The mixture is concentrated, and the residue is chromatographed (Biotage 40S, (1:499) MeOH:CH2Cl2). The product fractions are pooled and concentrated to afford 0.103 g (41%) of (3R)-3-(phenoxymethyl)-2,3-dihydro-1,4-benzodioxine-6-carboxylic acid as a solid. Example 12 is obtained in 45% yield as a monohydrate solid following the procedures outlined in Example 1, making non-critical changes: 1H NMR (400 MHz, CD3OD) δ 7.40-7.55, 7.25-7.35, 6.90-7.05, 4.35-4.65, 4.20-4.35, 3.75-3.90, 3.25-3.55, 2.30-2.40, 2.15-2.30, 2.05-2.15, 1.85-2.00; MS (EI) m/z 394 (M+).

Aufarbeitung

  1. temperatureto warm to rt overnight
  2. concentrationThe mixture is concentrated
  3. custompartitioned between EtOAc and H2O
  4. dry with materialthe organic layer dried (MgSO4)
  5. customchromatographed (Biotage 40S+SIM, (1:19) EtOAc:hexane)
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-3313d9aba95f483186abc0b5c5df759b
Quelldatensatz
uspto-grants-2005_10
Patentnummer
US06951868B2

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