1,2-Dimethoxyethane → HCID 67435904, compound

HRID 1968898Notes

Reaction equation

HRID 1968898 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([CH2:13][NH:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[C:20](Br)[CH:21]=2)[CH:16]=1)[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].[CH:27]1(B2OC(C)(C)C(C)(C)O2)[CH2:29][CH2:28]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COCCOC>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].O>[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([CH2:13][NH:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH:27]3[CH2:29][CH2:28]3)[CH:21]=2)[CH:16]=1)[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 67437669HCID 67437669, compound

Product 1

HCID 67435904HCID 67435904, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

{(1S,2S)-1-[(6-Bromo-naphthalen-2-ylamino)-methyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (210 mg, 0.5 mmol), 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (336 mg, 2.0 mmol), Pd(dppf)2Cl2 (82 mg, 0.1 mmol), K3PO4 (320 mg, 1.5 mmol) was combined in the mixture of DME (2.4 mL) and water (0.6 mL). The reaction mixture was heated at 130° C. for 10 mins under Microwave condition. The reaction mixture was cooled to r.t. and was quenched by the slow addition of 1N NaOH solution (15 mL). The reaction mixture was transferred to a separatory funnel containing water (20 mL). The aqueous layer was extracted with DCM (3×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated. The residue was purified on silica gel (7%→17% ethyl acetate in hexanes) to afford {(1S,2S)-1-[(6-cyclopropyl-naphthalen-2-ylamino)-methyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (107 mg, 60% yield) as a light brown solid: LC/MS (ESI) m/e 383.3 [(M+H)+, calcd for C24H34N2O2 382.6].

Workup

  1. temperatureThe reaction mixture was cooled to r.t.
  2. customwas quenched by the slow addition of 1N NaOH solution (15 mL)
  3. customThe reaction mixture was transferred to a separatory funnel
  4. additioncontaining water (20 mL)
  5. extractionThe aqueous layer was extracted with DCM (3×50 mL)
  6. washThe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on silica gel (7%→17% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2f7b048c69eb48708e0d1ca7c6392237
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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