Acetic Acid → {4-[(2S,4R)-1-Boc-4-(t-butyldimetylsilyl)oxypyrrolidin-2-ylmethyl]amino-2-phenylbenzoyl}methionine methyl ester

HRID 383122

Reaction equation

HRID 383122 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:26]([N:33]1[CH2:37][C@H:36]([O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:35][C@H:34]1[CH:46]=O)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH2:46][C@@H:34]2[CH2:35][C@@H:36]([O:38][Si:39]([C:42]([CH3:43])([CH3:44])[CH3:45])([CH3:41])[CH3:40])[CH2:37][N:33]2[C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])=[CH:9][C:8]=1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 18666758N-(4-Amino-2-phenylbenzoyl)methionine methyl ester2×

Product 1

HCID 70213927{4-[(2S,4R)-1-Boc-4-(t-butyldimetylsilyl)oxypyrrolidin-2-ylmethyl]amino-2-phenylbenzoyl}methionine methyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 0.75 g (2.09 mmol) of [2-phenyl-4-aminobenzoyl]methionine methyl ester (compound 8) and 0.7 g (2.1 mmol) of (2S,4R)-1-Boc-4-[t-butyldimethylsilyloxy]-pyrrolidin-2-aldehyde, prepared as in Example 171B, in 10 ml of methanol were added 1 ml of acetic acid, followed by 0.2 g (3.1 mmol) of sodium cyanoborohydride. The reaction mixture was stirred overnight. After removal of the solvent, the residue was partitioned with ethyl acetate and 5% sodium bicarbonate, and extracted 3 times with ethyl acetate. The combined organic solution was washed with water and brine, dried over magnesium sulfate, and solvent was removed. The residue was flash-chromatographed on silica gel (2:1 hexanes-ethyl acetate) to yield 261 mg (74%) of {4-[(2S,4R)-1-Boc-4-(t-butyldimetylsilyl)oxypyrrolidin-2-ylmethyl]amino-2-phenylbenzoyl}methionine methyl ester as a white solid: mp 48° C.; [α]25D−15.6 (c=1.03, CHCl3);

Workup

  1. customAfter removal of the solvent
  2. customthe residue was partitioned with ethyl acetate and 5% sodium bicarbonate
  3. extractionextracted 3 times with ethyl acetate
  4. washThe combined organic solution was washed with water and brine
  5. dry with materialdried over magnesium sulfate, and solvent
  6. customwas removed
  7. customThe residue was flash-chromatographed on silica gel (2:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-8fda9393fddd4117b1770a43cd252330
Source dataset
uspto-grants-2001_10
Patent number
US06310095B1

Linked notes

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