Ammonium Chloride → (R)-3-(5-(cyclohexylmethoxy)thiophen-2-yl)-3-hydroxypropanenitrile

HRID 63301Notes

Reaction equation

HRID 63301 reaction equation
[CH:1]1([CH2:7][O:8][C:9]2[S:13][C:12]([C:14](=[O:18])[CH2:15][C:16]#[N:17])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+].[Cl-]>C(O)=O.CCN(CC)CC>[CH:1]1([CH2:7][O:8][C:9]2[S:13][C:12]([C@H:14]([OH:18])[CH2:15][C:16]#[N:17])=[CH:11][CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 25517Ammonium ChlorideHCID 866945893-(5-(Cyclohexylmethoxy)thiophen-2-yl)-3-oxopropanenitrile

Product 1

HCID 86694588(R)-3-(5-(cyclohexylmethoxy)thiophen-2-yl)-3-hydroxypropanenitrile

Reagents, catalysts & solvents 1

HCID 11084032Triethylammonium formateSolvent

Procedure

(1R,2R)—RuCl(TsDPEN)(p-cymene) (6.3 mg, 0.01 mmol) was added to a degassed solution of 3-(5-(cyclohexylmethoxy)thiophen-2-yl)-3-oxopropanenitrile (4) (0.27 g, 1.03 mmol) in HCOOH:Et3N (1:1, 4.0 M in EtOH) and the reaction mixture was stirred at room temperature for 24 hrs. Aqueous NH4Cl (25%) was added and the mixture was extracted twice with MTBE. Combined organic layers were washed with brine and concentrated under reduced pressure. Purification by flash chromatography gave (R)-3-(5-(cyclohexylmethoxy)thiophen-2-yl)-3-hydroxypropanenitrile as an off-white solid which was used directly in the next step. Yield (0.21 g, 77%); 1H NMR (400 MHz, CD3OD) δ 6.64-6.78 (m, 1H), 6.02-6.10 (m, 1H), 4.99-5.09 (m, 1H), 3.79-3.88 (m, 2H), 2.79-2.91 (m, 2H), 1.62-1.90 (m, 6H), 1.12-1.39 (m, 3H), 0.98-1.12 (m, 2H).

Workup

  1. extractionthe mixture was extracted twice with MTBE
  2. washCombined organic layers were washed with brine
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0860ce323f6e4fe1b554e30e5703835e
Source dataset
uspto-grants-2016_09
Patent number
US09447078B2

Reaction notes

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