Sodium triacetoxyborohydride → HCID 117857475, compound

HRID 1483160Notes

Reaction equation

HRID 1483160 reaction equation
[CH:1]1([CH:5]=O)[CH2:4][CH2:3][CH2:2]1.[O:7]1[CH2:11][CH2:10][O:9][C:8]21[CH2:20][CH2:19][C@@H:18]1[C@@:13]34[C:27]5[C:22](=[CH:23][CH:24]=[C:25]([C:29]#[N:30])[C:26]=5[O:28][C@@H:12]23)[CH2:21][C@H:17]1[NH:16][CH2:15][CH2:14]4.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH:1]1([CH2:5][N:16]2[CH2:15][CH2:14][C@@:13]34[C:27]5[C:22]6[CH2:21][C@@H:17]2[C@@H:18]3[CH2:19][CH2:20][C:8]2([C@@H:12]4[O:28][C:26]=5[C:25]([C:29]#[N:30])=[CH:24][CH:23]=6)[O:7][CH2:11][CH2:10][O:9]2)[CH2:2][CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 12431621CyclobutanecarbaldehydeHCID 117857646HCID 117857646, compound

Product 1

HCID 117857475HCID 117857475, compoundYield 102.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of cyclobutane carboxaldehyde (19.45 g, 231.2 mmol) in dichloromethane (500 mL) was added (4R,4aR,7aR,12bS)-1,2,3,4,4a,5,6,7a-octahydrospiro[4,12-methanobenzofuro[3,2-e]isoquinoline-7,2′-[1,3]dioxolane]-9-carbonitrile (25 g, 77.1 mmol). The reaction was stirred for 60 minutes at room temperature before sodium triacetoxyborohydride (32.7 g, 154.0 mmol) was added portionwise over 20 minutes. After one hour, the reaction was quenched with NaHCO3 solution and extracted with dichloromethane (×3). The dichloromethane phases were combined, washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica chromatography eluted with dichloromethane to 7% methanol in dichloromethane to give (4R,4aR,7aR,12bS)-3-(cyclobutylmethyl)-1,2,3,4,4a,5,6,7a-octahydrospiro[4,12-methanobenzofuro[3,2-e]isoquinoline-7,2′-[1,3]dioxolane]-9-carbonitrile (31.1 g, 98% pure LCMS, assume quant.); [M+H]+ 393.1.

Workup

  1. additionwas added portionwise over 20 minutes
  2. customthe reaction was quenched with NaHCO3 solution
  3. extractionextracted with dichloromethane (×3)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica chromatography
  8. washeluted with dichloromethane to 7% methanol in dichloromethane

Sources & evidence

ORD record
ord-0646144344b74ff19218eaed9a95205d
Source dataset
uspto-grants-2016_08
Patent number
US09416137B2

Reaction notes

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