Dichloromethane → tert-butyl [2-[[3'-ethoxy-4'-[[(methylsulfonyl)amino]carbonyl]-4-biphenylyl]oxy]ethyl][(2R)-2-hydroxy-2-phenylethyl]carbamate

HRID 2220419Notes

Reaction equation

HRID 2220419 reaction equation
[OH:1][C@H:2]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][N:4]([CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[CH2:28]([O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[C:37]([NH:39][S:40]([CH3:43])(=[O:42])=[O:41])=[O:38])[CH3:29].ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN(C)C=O>[CH2:28]([O:30][C:31]1[CH:32]=[C:33]([C:18]2[CH:19]=[CH:20][C:15]([O:14][CH2:13][CH2:12][N:4]([CH2:3][C@H:2]([OH:1])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[CH:16][CH:17]=2)[CH:34]=[CH:35][C:36]=1[C:37]([NH:39][S:40]([CH3:43])(=[O:42])=[O:41])=[O:38])[CH3:29]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 67097763HCID 67097763, compoundHCID 69103071HCID 69103071, compound

Product 1

HCID 86598953tert-butyl [2-[[3'-ethoxy-4'-[[(methylsulfonyl)amino]carbonyl]-4-biphenylyl]oxy]ethyl][(2R)-2-hydroxy-2-phenylethyl]carbamateYield 27.3%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl [(2R)-2-hydroxy-2-phenylethyl][2-(4-iodophenoxy)ethyl]carbamate (250 mg), [3-ethoxy-4-[[(methylsulfonyl)amino]carbonyl]phenyl]boronic acid (223 mg), [1,1′-bis(diphenylphosphino]ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1, 114 mg), 1,1′-bis(diphenylphosphino)ferrocene (32 mg), N,N-dimethylformamide (5 ml), and 2N sodium carbonate solution (0.99 ml) was stirred at 80° C. for 1 hour. After cooling to room temperature, the mixture was quenched by the addition of 1N hydrochloric acid (1.99 ml) and partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was separated, washed with water (20 ml×2) and brine (20 ml), and dried over magnesium sulfate. Filtration followed by evaporation gave a brown foam which was chromatographed on silica gel (eluent: hexane/ethyl acetate) to give tert-butyl [2-[[3′-ethoxy-4′-[[(methylsulfonyl)amino]carbonyl]-4-biphenylyl]oxy]ethyl][(2R)-2-hydroxy-2-phenylethyl]carbamate (84.5 mg) as a pale orange solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was quenched by the addition of 1N hydrochloric acid (1.99 ml)
  3. custompartitioned between ethyl acetate (20 ml) and water (20 ml)
  4. customThe organic layer was separated
  5. washwashed with water (20 ml×2) and brine (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration
  8. customfollowed by evaporation
  9. customgave a brown foam which
  10. customwas chromatographed on silica gel (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-970a9310760c44c3bc5da8514c526e58
Source dataset
uspto-grants-2008_08
Patent number
US07417060B2

Reaction notes

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