Sodium triacetoxyborohydride → 2-[[2-[(9H-Fluoren-9-ylmethoxy)carbonyl]-1,2-dimethylhydrazinyl]methyl]-1H-indole-1-propanoic acid

HRID 628180Notes

Reaction equation

HRID 628180 reaction equation
[CH:1]([C:3]1[N:4]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)=O.[C:17]([N:34]([NH:36][CH3:37])[CH3:35])([O:19][CH2:20][CH:21]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:23]1[C:22]2[CH:21]([CH2:20][O:19][C:17]([N:34]([CH3:35])[N:36]([CH2:1][C:3]3[N:4]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])[C:5]4[C:10]([CH:11]=3)=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH3:37])=[O:18])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 17870033HCID 17870033, compound2×HCID 69099641HCID 69099641, compound

Product 1

HCID 867189802-[[2-[(9H-Fluoren-9-ylmethoxy)carbonyl]-1,2-dimethylhydrazinyl]methyl]-1H-indole-1-propanoic acidYield 62%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Compound 3 was synthesized from Compound 2 as follows. To a solution of Compound 2 (1.193 g, 5.492 mmol) and FmocN(Me)NHMe (2.147 g, 7.604 mmol, 1.38 equiv) in 1,2-dichloroethane (anhydrous, 25 mL) was added sodium triacetoxyborohydride (1.273 g, 6.006 mmol, 1.09 equiv). The resulting yellow suspension was stirred for 2 h and then quenched with sodium bicarbonate (saturated aqueous solution, 10 mL), followed by addition of hydrogen chloride (1 M aqueous solution) to pH 4. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (5×10 mL). The pooled organic extracts were dried over sodium sulfate, filtered, and concentrated to an orange oil. Purification by C18 silica gel chromatography (20-90% acetonitrile in water) yielded 3 as a waxy pink solid (1.656 g, 3.425 mmol, 62%). 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J=7.4 Hz, 2H), 7.70-7.47 (br m, 3H), 7.42-7.16 (br m, 6H), 7.12-7.05 (m, 1H), 6.37 (s, 0.6H), 6.05 (s, 0.4H), 4.75-4.30 (br m, 4H), 4.23 (m, 1H), 4.10 (br s, 1H), 3.55 (br d, 1H), 3.11-2.69 (m, 5H), 2.57 (br s, 2H), 2.09 (br s, 1H). 13C NMR (101 MHz, CDCl3) δ 174.90, 155.65, 143.81, 141.42, 136.98, 134.64, 127.75, 127.48, 127.12, 124.92, 122.00, 120.73, 120.01, 119.75, 109.19, 103.74, 67.33, 66.80, 51.39, 47.30, 39.58, 39.32, 35.23, 32.10. HRMS (ESI) calcd for C29H30N3O4 [M+H]+: 484.2236. found: 484.2222.

Workup

  1. customquenched with sodium bicarbonate (saturated aqueous solution, 10 mL)
  2. additionfollowed by addition of hydrogen chloride (1 M aqueous solution) to pH 4
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with dichloromethane (5×10 mL)
  5. dry with materialThe pooled organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an orange oil
  8. customPurification by C18 silica gel chromatography (20-90% acetonitrile in water)

Sources & evidence

ORD record
ord-b498b981ed0146f6aa54b9c5563b852f
Source dataset
uspto-grants-2016_04
Patent number
US09310374B2

Reaction notes

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