Lithium borohydride → Tert-butyl 2-{[4-(hydroxymethyl)benzoyl]amino}-4-thien-2-ylphenylcarbamate

HRID 1013517Notes

Reaction equation

HRID 1013517 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21]([C:23]1[CH:32]=[CH:31][C:26]([C:27](OC)=[O:28])=[CH:25][CH:24]=1)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[BH4-]>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21](=[O:22])[C:23]1[CH:24]=[CH:25][C:26]([CH2:27][OH:28])=[CH:31][CH:32]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 57607810Methyl 4-[({2-[(tert-butoxycarbonyl)amino]-5-thien-2-ylphenyl}amino)carbonyl]benzoate

Product 1

HCID 57607813Tert-butyl 2-{[4-(hydroxymethyl)benzoyl]amino}-4-thien-2-ylphenylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 4-[({2-[(tert-butoxycarbonyl)amino]-5-thien-2-ylphenyl}amino)carbonyl]benzoate (743 mg, 1.64 mmol) and anhydrous THF (0.10 M) was cooled to 0° C. and a solution of LiBH4 (5.49 mL, 11.0 mmol, 2M in THF) was added dropwise. The resulting solution was allowed to slowly warm to ambient temperature over 14 hours. The reaction was then cooled to 0° C. and quenched with saturated aqueous ammonium cloride. The mixture was diluted with water and extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by MPLC (SiO2, 10-80% EtOAc in hexanes) to afford a white glass: 1H-NMR (600 mHz, DMSO-d6) δ 9.87 (s, 1H), 8.73 (s, 1H), 7.92 (d, J=9.2 Hz, 2H), 7.81 (d, J=2.1 Hz, 1H), 7.58-7.42 (m, 5H), 7.11 (d, J=3.5 Hz, 1H), 7.10 (d, J=3.5 Hz, 1H), 5.34 (t, J=5.9 Hz, 1H), 4.57 (d, J=5.6 Hz, 2H), 1.43 (s, 9H).

Workup

  1. temperatureThe reaction was then cooled to 0° C.
  2. customquenched with saturated aqueous ammonium cloride
  3. additionThe mixture was diluted with water
  4. extractionextracted with ethyl acetate twice
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by MPLC (SiO2, 10-80% EtOAc in hexanes)
  9. customto afford a white glass

Sources & evidence

ORD record
ord-916d23749dd6401e8aaa08dc1839357b
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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