1,1-Dichloroethane → HCID 131734934, compound

HRID 921804Notes

Reaction equation

HRID 921804 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]3[CH2:14][C@H:15]([OH:17])[CH2:16][C@H:10]3[CH2:9]2)=[CH:6][C:5]([C:18]#[N:19])=[CH:4][C:3]=1[NH:20]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O.ClC(Cl)C>ClCCl>[NH2:20][C:3]1[CH:4]=[C:5]([CH:6]=[C:7]([N:8]2[CH2:13][CH2:12][N:11]3[CH2:14][C@H:15]([OH:17])[CH2:16][C@H:10]3[CH2:9]2)[C:2]=1[Cl:1])[C:18]#[N:19]

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acidHCID 131734935(+/-)-tert-butyl (2-chloro-5-cyano-3-((7R,8aS)-7-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)carbamate

Product 1

HCID 131734934HCID 131734934, compoundYield 79.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(+/−)-tert-butyl (2-chloro-5-cyano-3-((7R,8aS)-7-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)carbamate (Isomer B, 304 mg, 0.774 mmol) was treated with 25% TFA in dichloroethane (6 ml, 19.47 mmol) at room temperature for 1 h. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate/1N sodium hydroxide (pH 10). The aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g gold column, eluting with 2-5% 2 N ammonia in methanol/dichloromethane), (+/−)-3-amino-4-chloro-5-((7R,8aS)-7-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)benzonitrile (181 mg) was obtained as a white solid.

Workup

  1. washwashed with saturated sodium bicarbonate/1N sodium hydroxide (pH 10)
  2. extractionThe aqueous layer was extracted with dichloromethane two more times
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (24 g gold column, eluting with 2-5% 2 N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-60b5c60c5c5d42c7b924edc5c746164d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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