Borane;tetrahydrofuran → N-[3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-5-(hydroxymethyl)phenyl]-N-propylmethanesulfonamide

HRID 899455Notes

Reaction equation

HRID 899455 reaction equation
C(OC([NH:8][C:9]([CH3:37])([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([N:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:23][CH2:24][CH3:25])[CH:21]=1)[C:16](O)=[O:17])=O)(C)(C)C.B.C1COCC1>C1COCC1>[NH2:8][C:9]([CH3:37])([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:21]=[C:20]([N:22]([CH2:23][CH2:24][CH3:25])[S:26]([CH3:29])(=[O:28])=[O:27])[CH:19]=[C:15]([CH2:16][OH:17])[CH:14]=1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 588563373-({2-[(Tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoic acid2×

Product 1

HCID 67319197N-[3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-5-(hydroxymethyl)phenyl]-N-propylmethanesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoic acid (intermediate XI, 145 mg, 0.271 mmol) in THF (2 mL) cooled to 0° C. was added BH3-THF (1.356 mL, 1.356 mmol, 1 M in THP). After 10 min, the reaction mixture was allowed to warm to rt and stirred for 60 h. The reaction mixture was cooled back down to 0° C. and carefully quenched with MeOH. The mixture was concentrated to half its original volume and diluted with EtOAc and water. Following dilution, the organic layer was extracted, washed with sat. aq. NaHCO3 and brine, dried over sodium sulfate and concentrated in vacuo to provide N-[3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-5-(hydroxymethyl)phenyl]-N-propylmethanesulfonamide as a white foam. 1H NMR (400 MHz, CDCl3) δ 7.33 (s, 1H), 7.29 (s, 1H), 7.28-7.20 (m, 4H), 7.17-7.13 (m, 2H), 4.74 (s, 2H), 4.60-4.51 (m, 3H), 3.63 (t, J=7.2 Hz, 2H), 3.53 (A of AB, d, J=8.8 Hz, 1H), 3.43 (B of AB, d, J=8.8 Hz, 1H), 3.12 (A of AB, d, J=13.2 Hz, 1H), 2.93 (B of AB, d, J=13.2 Hz, 1H), 2.88 (s, 3H), 1.55-1.45 (m, 2H), 1.46 (s, 9H), 1.25 (s, 3H), 0.91 (t, J=7.3 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled back down to 0° C.
  2. customcarefully quenched with MeOH
  3. concentrationThe mixture was concentrated to half its original volume
  4. additiondiluted with EtOAc and water
  5. extractionthe organic layer was extracted
  6. washwashed with sat. aq. NaHCO3 and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e2bb77e9b5424f92a2f3bc4f0f32fd3e
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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