Acetic Acid → Ammonia

HRID 1364174Notes

Reaction equation

HRID 1364174 reaction equation
[NH2:1][CH2:2][C:3]([CH:5]1[C@@H:10]2[CH2:11][CH2:12][C@H:6]1[CH2:7][CH:8]([C@H:13]([NH:24][S@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:9]2)=[O:4].C(O)(=O)C.[CH3:35][C:36]([CH3:38])=O.C([BH3-])#N.[Na+]>CO>[NH3:1].[CH:36]([NH:1][CH2:2][C:3]([CH:5]1[C@@H:6]2[CH2:12][CH2:11][C@H:10]1[CH2:9][CH:8]([C@H:13]([NH:24][S@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:7]2)=[O:4])([CH3:38])[CH3:35]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5003444Sodium cyanoborohydrideHCID 66940034HCID 66940034, compound

Product 2

HCID 222AmmoniaHCID 66940004HCID 66940004, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To (S)-2-Methyl-propane-2-sulfinic acid [(R)-1-[(1S,5R)-8-(2-amino-acetyl)-bicyclo[3.2.1]oct-3-yl]-2-(2,4,5-trifluoro-phenyl)-ethyl]-amide (150 mg, 0.33 mmol) in methanol (3 mL) is added acetic acid until to have pH 5-5.5. After addition of acetone (124 uL, 1.68 mmol), the reaction is stirred at rt during 1 h and sodium cyanoborohydride (43 mg, 0.67 mmol) is added before stirring at rt during 16 h. The reaction is quenched with ethylacetate and an aqueous saturated NaHCO3 solution, the organic phase is dried and evaporated to afford the crude compound before purification onto a SCX-2 cartridge (5 g, DCM/MeOH 1:1, then 2N NH3 in MeOH) to yield the title compound.

Workup

  1. stirringbefore stirring at rt during 16 h
  2. customThe reaction is quenched with ethylacetate
  3. dry with materialan aqueous saturated NaHCO3 solution, the organic phase is dried
  4. customevaporated
  5. customto afford the crude compound
  6. custombefore purification onto a SCX-2 cartridge (5 g, DCM/MeOH 1:1

Sources & evidence

ORD record
ord-2ee288803a794281b8509cbc70b265a1
Source dataset
uspto-grants-2011_02
Patent number
US07888351B2

Reaction notes

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