Triethylamine → 6-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indole-1-carboxylic acid tert-butyl ester

HRID 551501Notes

Reaction equation

HRID 551501 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[C:4]([O:16][CH3:17])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:51]([O:55][C:56]([N:58]1[C:66]2[C:61](=[CH:62][CH:63]=[C:64]([CH2:67]O)[CH:65]=2)[CH:60]=[CH:59]1)=[O:57])([CH3:54])([CH3:53])[CH3:52].C(N(CC)CC)C>ClCCl>[C:51]([O:55][C:56]([N:58]1[C:66]2[C:61](=[CH:62][CH:63]=[C:64]([CH2:67][O:15][C:12]3[CH:11]=[CH:10][C:9]([C:5]4[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=4[O:16][CH3:17])=[CH:14][CH:13]=3)[CH:65]=2)[CH:60]=[CH:59]1)=[O:57])([CH3:54])([CH3:53])[CH3:52]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 23560816tert-Butyl 6-(hydroxymethyl)-1H-indole-1-carboxylateHCID 582599934',5'-Difluoro-2'-methoxy-biphenyl-4-ol

Product 1

HCID 671519286-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indole-1-carboxylic acid tert-butyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 4′,5′-difluoro-2′-methoxy-biphenyl-4-ol (472 mg, 2 mmol, 2 eq) was added polymer-bound triphenyl-phosphine (667 mg, 2 mmol, 2 eq) and dichloromethane (10 mL). The mixture was placed under nitrogen, cooled in an ice bath, diisopropyl azodicarboxylate (0.394 mL, 2 mmol, 2 eq) was added drop-wise, stirred for 1.5 hr. A solution of 6-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester (247 mg, 1 mmol, 1 eq) and triethylamine (0.279 mL, 2 mmol, 2 eq) in dichloromethane (2 mL) was added drop to portion wise and the reaction allowed to warm to room temperature overnight (20 hr). The reaction was filtered over Celite, adsorbed onto silica gel, and purified by flash chromatography with a gradient from 1-15% ethyl acetate in hexanes to yield 6-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indole-1-carboxylic acid tert-butyl ester white/clear solid (288 mg, 62%). LC-MS (ES) calculated for C27H25F2NO2, 465.2; found m/z 466 [M+H]+.

Workup

  1. temperaturecooled in an ice bath
  2. filtrationThe reaction was filtered over Celite
  3. custompurified by flash chromatography with a gradient from 1-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-cf1e06e22be74a118288876d3ebb2712
Source dataset
uspto-grants-2011_05
Patent number
US07947728B1

Reaction notes

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