Acetone → HCID 86596955, compound

HRID 2225270Notes

Reaction equation

HRID 2225270 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@@H:6]([C:8]([OH:10])=[O:9])[C@@H:5]([NH:11][C:12](=[O:28])[CH2:13][NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=2)[CH2:4][CH2:3]1.C(Cl)Cl.[BH-](OC(C)=O)(OC(C)=O)O[C:34](C)=O.[Na+].C=O.[CH3:48][C:49]([CH3:51])=O>C(O)(=O)C>[C:23]([C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[OH:22])[C:15]([NH:14][CH2:13][C:12]([NH:11][C@H:5]1[CH2:4][CH2:3][C@@H:2]([N:1]([CH:49]([CH3:51])[CH3:48])[CH3:34])[CH2:7][C@H:6]1[C:8]([OH:10])=[O:9])=[O:28])=[O:27])([CH3:24])([CH3:25])[CH3:26]

Participants

7

Reactant 5

HCID 180AcetoneHCID 712FormaldehydeHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydride2×HCID 86596956HCID 86596956, compound

Product 1

HCID 86596955HCID 86596955, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of (1R,2S,5R)-5-amino-2-(2-(3-tert-butyl-4-hydroxybenzamido)acetamido)cyclohexanecarboxylic acid (67 mg, 0.17 mmol) in anhyd CH2Cl2 (1 mL) and acetone (1 mL) was added acetic acid (0.5 mL) and NaBH(OAc)3 (110 mg, 0.51 mmol) and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in CH2Cl2 (1 mL) and CH3CN (1 mL). To this solution was added formaldeyde (4 mL, 37% in water) and NaBH(OAc)3 (200 mg, 0.84 mmol) in five portions over 10 h. The reaction mixture was stirred at room temperature for 12 h and then concentrated in vacuo to dryness. The residue was dissolved in water and purified by semi-preparative HPLC to give (1R,2S,5R)-2-(2-(3-tert-butyl-4-hydroxybenzamido)acetamido)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid (22.4 mg, 29% over 3 steps) as a white powder: 1H NMR (300 MHz, CD3OD) δ 7.95 (s, 1H), 7.78 (s, 1H), 7.58-7.54 (m, 1H), 6.80-6.77 (m, 1H), 4.55 (s, 1H), 4.08-3.91 (m, 3H), 3.90-3.71 (m, 1H), 3.69-3.45 (m, 1H), 2.92-2.85 (m, 1H), 2.79 (s, 3H), 2.15-1.55 (m, 7H), 1.41-1.33 (m, 15H); MS found: (M+H)+=448.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in CH2Cl2 (1 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 12 h
  4. concentrationconcentrated in vacuo to dryness
  5. dissolutionThe residue was dissolved in water
  6. custompurified by semi-preparative HPLC

Sources & evidence

ORD record
ord-8d84aa4eea8944358e26d91e7c795d02
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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