Triethylamine → N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-1-methane sulfonyloxybutane

HRID 1281198Notes

Reaction equation

HRID 1281198 reaction equation
C[O:2][C:3](=O)[C@H:4]([OH:21])[C@@H:5]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[BH4-].[Na+].[CH3:25][S:26](Cl)(=[O:28])=[O:27].C(N(CC)CC)C>C(OCC)(=O)C>[C:17]([O:16][C:14]([NH:13][C@@H:5]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C@@H:4]([OH:21])[CH2:3][O:2][S:26]([CH3:25])(=[O:28])=[O:27])=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 4311764Sodium borohydrideHCID 11449720N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenylbutyric acid methyl ester

Product 1

HCID 10904464N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-1-methane sulfonyloxybutaneYield 200.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-butyric acid methyl ester 340.4 kg was reduced with sodium borohydride by the same way as described in Reference Example 3, to obtain the crude N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-1-butanol, which was dissolved in ethyl acetate 988 kg. To the solution were added methane sulfonylchloride 130.7 kg at 15-0° C. and triethylamine 115.4 kg, successively, and the solution was stirred at 20-30° C. for 15 min. The reaction solution was washed with aqueous 5% sodium bicarbonate solution to separate an organic phase, which was washed with aqueous 10% sodium chloride solution. The separated organic phase was mixed with n-heptane and cooled gradually down to 5° C. or lower to deposit crystals, which were filtered by a Nutsche funnel to obtain a wet crystal of crude N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-1-methanesulfonyloxybutane 793 kg (Net.368.9 kg).

Workup

  1. customto obtain the crude N-tert-butoxycarbonyl-3(S)-amino-2(R)-hydroxy-4-phenyl-1-butanol, which
  2. washThe reaction solution was washed with aqueous 5% sodium bicarbonate solution
  3. customto separate an organic phase, which
  4. washwas washed with aqueous 10% sodium chloride solution
  5. additionThe separated organic phase was mixed with n-heptane
  6. filtrationwere filtered by a Nutsche funnel

Sources & evidence

ORD record
ord-dc283695b2d546b693d55c497160b84a
Source dataset
uspto-grants-2002_09
Patent number
US06452026B1

Reaction notes

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