Toluene → 5'-((1R,2R)-1-Benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2'-fluoro-biphenyl-2-carboxylic acid t-butyl ester

HRID 2361127Notes

Reaction equation

HRID 2361127 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1B1OC(C)(C)C(C)(C)O1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.[CH2:30]([O:32][C:33](=[O:55])[C@H:34]([OH:54])[C@H:35]([NH:43][C:44](=[O:53])[C:45]1[CH:50]=[CH:49][C:48]([F:51])=[C:47](Br)[CH:46]=1)[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH3:31].C([O-])([O-])=O.[K+].[K+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[C:1]([O:5][C:6]([C:8]1[C:9]([C:47]2[CH:46]=[C:45]([C:44](=[O:53])[NH:43][C@H:35]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C@H:34]([C:33]([O:32][CH2:30][CH3:31])=[O:55])[OH:54])[CH:50]=[CH:49][C:48]=2[F:51])=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 4376764Tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 71073975(2R,3R)-3-(3-bromo-4-fluoro-benzoylamino)-2-hydroxy-4-phenyl-butyric acid ethyl ester

Product 1

HCID 710736115'-((1R,2R)-1-Benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2'-fluoro-biphenyl-2-carboxylic acid t-butyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

2-t-Butoxycarbonylphenylboronic acid pinacol ester (173 mg, 568 μmol, 1.2 eq.) and toluene (661 μL) were added to (2R,3R)-3-(3-bromo-4-fluoro-benzoylamino)-2-hydroxy-4-phenyl-butyric acid ethyl ester (201 mg, 474 μmol, 1.0 eq.), followed by EtOH (361 μL) then K2CO3 (131 mg, 947 μmol, 2.0 eq.) predissolved in water (124 μL). The mixture was stirred to aid in dissolution. The reaction vessel was purged with nitrogen then Pd(PPh3)4 (54.7 mg, 47.4 μmol) was added quickly. The reaction vessel was capped and heated to 100° C. for 30 minutes. The organics were removed and evaporated under vacuum to yield 5′-((1R,2R)-1-benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2′-fluoro-biphenyl-2-carboxylic acid t-butyl ester.

Workup

  1. dissolutionto aid in dissolution
  2. customThe reaction vessel was purged with nitrogen
  3. customThe reaction vessel was capped
  4. customThe organics were removed
  5. customevaporated under vacuum

Sources & evidence

ORD record
ord-59efc447aafd4f23b12d2f06147f11b4
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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