Ethanol → 1-[N-[(3S)-3-(Benzoylamino)-2-[[(4-methoxyphenyl)methyl]thio]-4-phenylbutyl]-L-alanyl]-L-proline, 1,1-dimethylethyl ester

HRID 637860Notes

Reaction equation

HRID 637860 reaction equation
[C:1]([NH:9][CH:10]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:11]([S:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH:12]=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:31][C@H:32]([C:34]([N:36]1[CH2:47][CH2:46][CH2:45][C@H:37]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:35])[CH3:33].C(O)C.C([BH3-])#N.[Na+]>O1CCCC1>[C:1]([NH:9][C@@H:10]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:11]([S:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH2:12][NH:31][C@H:32]([C:34]([N:36]1[CH2:47][CH2:46][CH2:45][C@H:37]1[C:38]([O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:39])=[O:35])[CH3:33])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 5003444Sodium cyanoborohydrideHCID 12939800tert-Butyl L-alanyl-L-prolinateHCID 56630203HCID 56630203, compound

Product 1

HCID 135019021-[N-[(3S)-3-(Benzoylamino)-2-[[(4-methoxyphenyl)methyl]thio]-4-phenylbutyl]-L-alanyl]-L-proline, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-β-(benzoylamino)-α-[[(4-methoxyphenyl)methyl]thio]-benzenebutanal (isomer A) (0.45 g., 1.07 mmole), L-alanyl-L-proline, 1,1-dimethylethyl ester (0.78 g., 3.21 mmole), and crushed 3A° molecular sieves (2 g.) in tetrahydrofuran (5 ml.) and absolute ethanol (5 ml.) is stirred at room temperature under argon. After 2.5 hours, sodium cyanoborohydride (0.20 g., 3 eq.) is added and stirring continued for 15 hours. The reaction mixture is filtered to remove the sieves and the filtrate is diluted with ethyl acetate and washed with water, 1N hydrochloric acid (twice), 1N sodium bicarbonate, and brine. After drying over anhydrous MgSO4, the solvent is removed to give the desired product, as a mixture of diastereomers, as a pale yellow oil. TLC (silica gel, benzene:acetone, 4:1) isomer A at Rf =0.30 and isomer B at Rf =0.13. Flash chromatography (silica gel LPS-1; benzene:acetone, 7:3) affords impure product (isomer A). Repeated flash chromatography (silica gel LPS-1; ethyl acetate:benzene, 6:4) gives 0.20 g. of 1-[N-[(3S)-3-(benzoylamino)-2-[[(4-methoxyphenyl)methyl]thio]-4-phenylbutyl]-L-alanyl]-L-proline, 1,1-dimethylethyl ester (isomer A) as a nearly colorless oil.

Workup

  1. waitcontinued for 15 hours
  2. filtrationThe reaction mixture is filtered
  3. customto remove the sieves
  4. additionthe filtrate is diluted with ethyl acetate
  5. washwashed with water, 1N hydrochloric acid (twice), 1N sodium bicarbonate, and brine
  6. dry with materialAfter drying over anhydrous MgSO4
  7. customthe solvent is removed

Sources & evidence

ORD record
ord-7ec3486974cf4d80bcd0624665e89265
Source dataset
uspto-grants-1985_12
Patent number
US04558150

Reaction notes

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