Ammonium Chloride → rac-ethyl 2-((4S,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate

HRID 1748810Notes

Reaction equation

HRID 1748810 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][CH:13]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:12]([CH3:21])=[N:11][C:10]3[N:22]([CH3:26])[N:23]=[C:24]([CH3:25])[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1.[BH4-].[Na+].[NH4+].[Cl-]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[S:14][C@@H:13]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C@@H:12]([CH3:21])[NH:11][C:10]3[N:22]([CH3:26])[N:23]=[C:24]([CH3:25])[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[S:14][C@@H:13]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C@@H:12]([CH3:21])[NH:11][C:10]3[N:22]([CH3:26])[N:23]=[C:24]([CH3:25])[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86724138ethyl 2-(4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate

Product 2

HCID 136634675rac-ethyl 2-((4R,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetateYield 19%HCID 136634681rac-ethyl 2-((4S,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetateYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl 2-(4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate (0.85 g, 1.97 mmol) in MeOH (3.94 mL) was cooled to about 0° C. To the reaction mixture was added sodium tetrahydroborate (0.298 g, 7.88 mmol) portionwise. The reaction mixture was allowed to slowly warm to ambient temperature and stirred for about 16 h. The reaction mixture was cooled to about 0° C. and then saturated aqueous NH4Cl (10 mL) was added. The mixture was partially concentrated under reduced pressure and EtOAc (20 mL) was added. The layers were separated and the aqueous layer was back extracted with EtOAc (10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, EtOAc/DCM 100:0 to 0:50) to afford rac-ethyl 2-((4R,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate (0.15 g, 0.37 mmol, 19%) LC-MS (Table 1, Method g) Rt=2.58, m/z 408 (M+H)+and rac-ethyl 2-((4S,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate (0.39 g, 0.97 mmol, 49%) LC-MS (Table 1, Method g) Rt=2.48, m/z 408 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to about 0° C.
  2. concentrationThe mixture was partially concentrated under reduced pressure and EtOAc (20 mL)
  3. additionwas added
  4. customThe layers were separated
  5. extractionthe aqueous layer was back extracted with EtOAc (10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by column chromatography (SiO2, EtOAc/DCM 100:0 to 0:50)

Sources & evidence

ORD record
ord-a4dfb2de52934e6eb97cc443576b5954
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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