Methane → (S)-Methyl 1-(1,3-benzodioxol-5-yl)-3-[4-methoxy-2-(phenylmethoxy)phenyl]-5-propoxy-1H-indene-2-carboxylate

HRID 277495Notes

Reaction equation

HRID 277495 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C@H:10]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=4)[C:12](OS(F)(=O)=O)=[C:11]3[C:28]([O:30][CH3:31])=[O:29])=[CH:9][C:4]=2[O:3][CH2:2]1.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[C:36]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:35]=1.C([O-])([O-])=O.[K+].[K+].C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.C1(C)C=CC=CC=1>[CH3:31][O:30][C:28]([C:11]1[C@@H:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)[C:18]2[C:13]([C:12]=1[C:37]1[CH:38]=[CH:39][C:34]([O:33][CH3:32])=[CH:35][C:36]=1[O:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=2)=[O:29]

Participants

8

Reactant 4

HCID 297Methane2×HCID 11430Potassium CarbonateHCID 11123220(S)-Methyl-1-(1,3-benzodioxol-5-yl)-3-[(fluorosulfonyl)oxy]5-propoxy-1H-indene-2-carboxylateHCID 118320852-(Benzyloxy)-4-methoxyphenylboronic acid2×

Product 1

HCID 11006267(S)-Methyl 1-(1,3-benzodioxol-5-yl)-3-[4-methoxy-2-(phenylmethoxy)phenyl]-5-propoxy-1H-indene-2-carboxylateYield 99.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A 50 mL three-necked flask under nitrogen was charged with (S)-methyl 1-(1,3-benzodioxol-5-yl)-3-[(fluorosulfonyl)oxy]-5-propoxy-1H-indene-2-carboxylate (600 mg, 1.3 mmol), [4-methoxy-2-(phenylmethoxy)phenyl]boronic acid (Compound (u)) (330 mg, 1.4 mmol), toluene (16 mL), EtOH (2 mL), and Pd(dppf)Cl2 catalyst (4.8 mg, 0.005 mmol). The mixture was stirred for 0.5 h at room temperature followed by the addition of 1.3 M K2CO3 solution (2.0 mL, 2.6 mmol) and heated to 70° C. for 45 min. The mixture was cooled to room temperature, charged with Norit A charcoal (5 g) and filtered through celite (10 g). The filtrate was then concentrated in vacuo affording (S)-methyl-1-(1,3-benzodioxol-5-yl)-3-[4-methoxy-2-(phenylmethoxy)phenyl]-5-propoxy-1H-indene-2-carboxylate as a yellow gum (731 mg, 99% yield). (viii)a. (S)-Methyl 1-(1,3-benzodioxol-5-yl)-3-[4-methoxy-2-(phenylmethoxy)phenyl]-S-propoxy-1H-indene-2-carboxylate A 500 mL three-necked round-bottomed flask under nitrogen was charged with (S) -Methyl-1-(1,3-benzodioxol-5-y)-3-[(fluorosulfonyl)oxy]5-propoxy-1H-indene-2-carboxylate (10 g, 21.46 mmol), [4-methoxy-2-(phenylmethoxy)phenyl]boronic acid (Compound (u)) (5.53 g, 21.46 mmol), toluene (200 mL), EtOH (16 mL), and Pd(dppf)Cl2 catalyst (78.5 mg, 0.11 mmol). The mixture was stirred for 0.5 h at room temperature followed by the addition of K2CO3 solution (5.92 g in 16 mL H,O, 42.92 mmol) and heated to 70° C. for 45 min. The mixture was cooled to room temperature, washed with H2O (2×50 mL), brine (1×50 mL), dried over MgSO4 and the solvent removed in vacuo. The crude product was purified via recrystallization from 2-methoxy ethanol to afford (S)-Methyl 1-(1,3-benzodioxol-5-yl)-3-[4-methoxy-2-(phenylmethoxy)phenyl]-5-propoxy-1H-indene-2-carboxylate as a light yellow solid (8.7 g, 75% yield): mp 114.0-117.0° C. 1H NMR (DMSO, 335 K) δ7.3-7.2 (m, 8H), 7.1 (d, J=8.3 Hz, 1H), 6.9 (dd, J=2.4, 8.2 Hz, 1H), 6.85 (d, J=2.1 Hz, 1H), 6.75 (dd, J=2.3, 8.2 Hz, 1H), 6.65 (d, J=2.3 Hz, 1H), 6.55 ; (d, J=1.5 Hz, 1H), 5.9 (s, 2H), 5.1 (s, 2H), 4.9 (s, 1H), 3.9-3.8 (m, 5H), 3.4 (s, 3H), 1.65 (quintet, J=7.8 Hz, 2H), 0.9 (t, J=7.4 Hz, 3H)

Workup

  1. temperatureheated to 70° C. for 45 min
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through celite (10 g)
  4. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-c47bd3f574484cbc97b2ebfb5c2004aa
Source dataset
uspto-grants-2002_03
Patent number
US06355813B1

Reaction notes

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