Sodium Bromide → Telaprevir

HRID 540980Notes

Reaction equation

HRID 540980 reaction equation
[CH:1]1([C@H:7]([NH:41][C:42]([C:44]2[CH:49]=[N:48][CH:47]=[CH:46][N:45]=2)=[O:43])[C:8]([NH:10][C@@H:11]([C:37]([CH3:40])([CH3:39])[CH3:38])[C:12]([N:14]2[CH2:18][C@@H:17]3[CH2:19][CH2:20][CH2:21][C@@H:16]3[C@H:15]2[C:22]([NH:24][C@@H:25]([CH2:34][CH2:35][CH3:36])[C@@H:26]([OH:33])[C:27]([NH:29][CH:30]2[CH2:32][CH2:31]2)=[O:28])=[O:23])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br-].[Na+].C(=O)(O)[O-].[Na+].CC1(C)N([O])C(C)(C)CCC1.Cl[O-].[Na+]>ClCCl.O>[CH:1]1([C@H:7]([NH:41][C:42]([C:44]2[CH:49]=[N:48][CH:47]=[CH:46][N:45]=2)=[O:43])[C:8]([NH:10][C@@H:11]([C:37]([CH3:38])([CH3:39])[CH3:40])[C:12]([N:14]2[CH2:18][C@@H:17]3[CH2:19][CH2:20][CH2:21][C@@H:16]3[C@H:15]2[C:22]([NH:24][C@@H:25]([CH2:34][CH2:35][CH3:36])[C:26](=[O:33])[C:27]([NH:29][CH:30]2[CH2:31][CH2:32]2)=[O:28])=[O:23])=[O:13])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 2724126TempoHCID 23665760Sodium HypochloriteHCID 59235547(1s,3ar,6as)-2-[(2s)-2-({(2s)-2-Cyclohexyl-2-[(Pyrazin-2-Ylcarbonyl)amino]acetyl}amino)-3,3-Dimethylbutanoyl]-N-[(2r,3s)-1-(Cyclopropylamino)-2-Hydroxy-1-Oxohexan-3-Yl]octahydrocyclopenta[c]pyrrole-1-Carboxamide

Product 1

HCID 3010818Telaprevir

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Compound 45 (2.0 g, 2.9 mmol) was dissolved in dichloromethane (14 mL), and to this solution was added a solution of sodium bromide (144 mg) in water (1.0 mL) followed by a solution of sodium bicarbonate (300 mg) in water (4.0 mL). The mixture was cooled to 0° C., whereupon TEMPO (53 mg, 0.34 mmol) was added. Commercial bleach solution containing sodium hypochlorite (3.3 mL) further diluted with water (9.6 mL) was added drop-wise over the course of 10 minutes. The mixture was stirred 1.5 hours at 5° C. after which the organic layer was separated and washed with 10% aqueous sodium sulfite (8 mL) then brine. The resulting solution was dried over magnesium sulfate, filtered, and then concentrated to dryness. After crystallization from dichloromethane/ethyl acetate, compound 4 showed spectroscopic properties identical to those reported in Example 14.

Workup

  1. additionwas added
  2. additionwas added drop-wise over the course of 10 minutes
  3. customwas separated
  4. washwashed with 10% aqueous sodium sulfite (8 mL)
  5. dry with materialThe resulting solution was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customAfter crystallization from dichloromethane/ethyl acetate, compound 4 showed spectroscopic properties identical to

Sources & evidence

ORD record
ord-d516ced2abbe42b99308bde6b7054a3c
Source dataset
uspto-grants-2014_10
Patent number
US08871904B2

Reaction notes

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