Sodium t-butoxide → HCID 68674938, compound

HRID 644029Notes

Reaction equation

HRID 644029 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[CH2:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1Br)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.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>[C:1]([O:5][C:6]([N:8]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[O:11][CH2:10][C@H:9]1[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 68675510HCID 68675510, compound

Product 1

HCID 68674938HCID 68674938, compoundYield 67.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of (R)-2-(2-tert-butoxycarbonylamino-2-cyclohexylethoxy)bromobenzene (500 mg, 1.26 mmol), tetrakis(triphenylphosphine)palladium(0) (146 mg, 0.126 mmol) and sodium tert-butoxide (181 mg 1.88 mmol) in toluene (4.0 ml) was exposed to microwave irradiation for 10 min at 120° C. The resulting mixture was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane and combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography eluting with 0-17% (v/v) ethyl acetate in heptane to afford (R)-4-tert-butoxycarbonyl-3-cyclohexyl-3,4-dihydro-2H-1,4-benzoxazine (270 mg, 0.85 mmol). This reaction was repeated 13 times on the same scale to afford the same intermediate (a total of 3.98 g, 12.5 mmol).

Workup

  1. customirradiation for 10 min at 120° C
  2. customThe resulting mixture was partitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washwere washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography
  8. washeluting with 0-17% (v/v) ethyl acetate in heptane

Sources & evidence

ORD record
ord-179b4324e7204268b05271764f078bf7
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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