Triethylamine → (3S,4S)-3-[3-(4-methanesulfonyl-benzyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2234209Notes

Reaction equation

HRID 2234209 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:24]=[CH:23][C:9]([CH2:10][N:11]2[C:15](=[O:16])[C:14]3([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[NH:13][C:12]2=[O:22])=[CH:8][CH:7]=1)(=[O:5])=[O:4].C(N(CC)CC)C.[C:32]([O:36][C:37]([N:39]1[CH2:43][C@H:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:41]([CH:50]=O)[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:32]([O:36][C:37]([N:39]1[CH2:43][C@H:42]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:41]([CH2:50][N:19]2[CH2:18][CH2:17][C:14]3([NH:13][C:12](=[O:22])[N:11]([CH2:10][C:9]4[CH:8]=[CH:7][C:6]([S:3]([CH3:2])(=[O:5])=[O:4])=[CH:24][CH:23]=4)[C:15]3=[O:16])[CH2:21][CH2:20]2)[CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 58981949(3R,4S)-3-formyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 686263323-(4-Methanesulfonyl-benzyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione hydrochloride

Product 1

HCID 11628596(3S,4S)-3-[3-(4-methanesulfonyl-benzyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 187 mg (0.50 mmol) of 3-(4-methanesulfonyl-benzyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione hydrochloride was added 5 mL of DCM followed by 0.066 mL of triethylamine (0.50 mmol) and a solution of (3R,4S)-3-formyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.93 mL of a 148 mg/mL solution, 0.50 mmol). The solution was stirred at room temperature for 30 minutes and sodium triacetoxyborohydride was added (159 mg, 0.75 mmol). The solution was stirred overnight. The resulting mixture was evaporated to dryness and purified by chromatography on Bond Elute™ (10 g) using 1:1 EtOAc:Hexane followed by 1% methanol in DCM. After evaporation of the desired fractions, 93 mg (31%) of (3S,4S)-3-[3-(4-methanesulfonyl-benzyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a white solid were obtained.

Workup

  1. stirringThe solution was stirred overnight
  2. customThe resulting mixture was evaporated to dryness
  3. custompurified by chromatography on Bond
  4. washElute™ (10 g)
  5. customAfter evaporation of the desired fractions

Sources & evidence

ORD record
ord-a3ae5914ae214f3ebe93869984b9ac6e
Source dataset
uspto-grants-2010_05
Patent number
US07709642B2

Reaction notes

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