Acetone → HCID 67323975, compound

HRID 518142Notes

Reaction equation

HRID 518142 reaction equation
[ClH:1].[C:2]1([S:8]([C:11]2[CH:12]=[CH:13][C:14]3[CH:23]4[CH:19]([NH:20][CH2:21][CH2:22]4)[CH2:18][O:17][C:15]=3[CH:16]=2)(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][C:25](=O)[CH3:26].C([BH3-])#N.[Na+].C1COCC1>ClCCCl.CO.C(O)(=O)C>[ClH:1].[C:2]1([S:8]([C:11]2[CH:12]=[CH:13][C:14]3[CH:23]4[CH:19]([N:20]([CH:25]([CH3:26])[CH3:24])[CH2:21][CH2:22]4)[CH2:18][O:17][C:15]=3[CH:16]=2)(=[O:10])=[O:9])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 67324032HCID 67324032, compound

Product 1

HCID 67323975HCID 67323975, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 22134543HCID 22134543, compoundSolvent

Procedure

7-(Phenylsulfonyl)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-b]pyrrole hydrochloride (enantiomer 1, Example 55, 20 mg, 0.08 mmol) was dissolved in 500 μL DCE:MeOH (9:1). After 10 min stirring, propan-2-one (7 μL, 1.5 eq), a 1 M solution of sodium cyanoborohydride in THF (0.16 mL, 0.16 mmol) and acetic acid (50 μL) were added sequentially. After stirring for 16 h, the reaction mixture was passed through a plug of silica gel and the solvent was evaporated. The residue was purified by preparative LC/MS using the standard procedure. The resulting material was dissolved in a small amount of DCM, treated with 1.0 N HCl in diethyl ether and the solvent evaporated to provide 7-(phenylsulfonyl)-3-(propan-2-yl)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-b]pyrrole hydrochloride. MS m/z 358.1 [M+H]+. 1H-NMR (400 MHz, DMSO-d6): δ 1.30 (d, J=1.6 Hz, 3H), 1.35 (d, J=1.6 Hz, 3H), 1.83-1.88 (m, 1H), 2.62-2.66 (m, 1H), 3.21-3.24 (m, 1H), 3.37 (bs, 1H), 3.66-3.72 (m, 2H), 4.10-4.24 (m, 3H), 4.23-4.41 (m, 1H), 7.45 (s, 1H), 7.52-7.77 (m, 5H), 7.97 (d, J=2 Hz 1H), 10.4 (bs, 1H).

Workup

  1. stirringAfter stirring for 16 h
  2. customthe solvent was evaporated
  3. customThe residue was purified by preparative LC/MS
  4. dissolutionThe resulting material was dissolved in a small amount of DCM
  5. additiontreated with 1.0 N HCl in diethyl ether
  6. customthe solvent evaporated

Sources & evidence

ORD record
ord-36f491c6f4c94335a15e84dd83f458af
Source dataset
uspto-grants-2015_08
Patent number
US09115147B2

Reaction notes

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