2-Methoxypropene → HCID 71230557, compound

HRID 401835Notes

Reaction equation

HRID 401835 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]#[C:8][C:9]([CH3:12])([CH3:11])[CH3:10])[S:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].CO[C:19]([CH3:21])=[CH2:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.CCOC(C)=O.C(O)(=O)C>[CH3:10][C:9]([CH3:11])([CH3:12])[C:8]#[C:7][C:5]1[S:4][C:3]([C:13]([O:15][CH3:16])=[O:14])=[C:2]([NH:1][CH:19]([CH3:21])[CH3:20])[CH:6]=1

Participants

8

Reactant 4

HCID 83002-MethoxypropeneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 24989346Methyl 3-amino-5-(3,3-dimethylbut-1-yn-1-yl)thiophene-2-carboxylate

Product 1

HCID 71230557HCID 71230557, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 3-amino-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate (see WO 2008058393) (12.0 g, 50.6 mmol) in dichloromethane (150 mL) was placed in a cool water bath (12 deg C.) and treated dropwise with 2-methoxyprop-1-ene (14.6 mL, 152 mmol) over about 6 minutes followed by acetic acid (8.7 mL) over about 5 minutes. Sodium triacetoxyborohydride (16.1 g, 152 mmol) was added portionwise over about 30 minutes. The reaction mixture was allowed to warm to ambient temperature and was stirred for 16 h. The resulting light orange solution was poured into cold sodium bicarbonate (sat aq, 200 mL). The organic layer was separated and the aqueous layer was extracted twice with dichloromethane (150 mL each). The combined organic layers were washed with sodium bicarbonate (sat aq) and brine, dried over sodium sulfate (anhyd), filtered and concentrated to an orange oil. Silica gel chromatography (0-15% EtOAc:Hex) afforded 13.0 g (92% yield) of the desired methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)thiophene-2-carboxylate as a light yellow oil which solidified upon standing to a waxy crystalline solid, and was used in the subsequent step.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted twice with dichloromethane (150 mL each)
  3. washThe combined organic layers were washed with sodium bicarbonate (sat aq) and brine
  4. dry with materialdried over sodium sulfate (anhyd)
  5. filtrationfiltered
  6. concentrationconcentrated to an orange oil

Sources & evidence

ORD record
ord-3757e743ce534a93bc37d5c65b3187db
Source dataset
uspto-grants-2014_06
Patent number
US08741946B2

Reaction notes

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