Toluene → ((1S,2S,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester

HRID 500014Notes

Reaction equation

HRID 500014 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([C@@H:13]([OH:28])[CH2:14][C@H:15]([CH2:19][O:20]CC2C=CC=CC=2)[CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([CH:29]([CH3:31])[CH3:30])[C@@H:9]1[C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34]([O:40][CH2:41][CH2:42][CH2:43][O:44][CH3:45])[CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na].[Cl-].[NH4+].C1(C)C=CC=CC=1>O1CCCC1.N.O.C(O)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:12]([CH2:11][C@H:10]([CH2:9][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34]([O:40][CH2:41][CH2:42][CH2:43][O:44][CH3:45])[CH:33]=1)[CH:29]([CH3:31])[CH3:30])[C@@H:13]([OH:28])[CH2:14][C@H:15]([CH2:19][OH:20])[CH:16]([CH3:17])[CH3:18])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 67304985(2R,3S,5S)-5-((1S,3S)-3-Benzyloxymethyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11678270((1S,2S,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl esterYield 88.4%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 222AmmoniaSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1.0 g of the pyrrolidine 8 in 2.5 mL of tetrahydrofuran is added to a mixture of 0.37 g of sodium in 5 mL of ammonia and 2.5 mL of tetrahydrofuran at −50° C. The mixture is stirred for 3 h then 2.56 g of ammonium chloride is added and the mixture allowed to warm to r.t. To the mixture is then added 40 mL of toluene, 1.9 g of acetic acid and 25 mL of water. The phases are separated and the aqueous phase is back-extracted with 25 mL of toluene. The combined organic phases are then washed with 4×120 mL of 1:1 water-brine, dried over sodium sulfate and the solvent removed in vacuum, affording e.g. 0.76 g of the product 9a as an oil.

Workup

  1. customThe phases are separated
  2. extractionthe aqueous phase is back-extracted with 25 mL of toluene
  3. washThe combined organic phases are then washed with 4×120 mL of 1:1 water-brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent removed in vacuum

Sources & evidence

ORD record
ord-c99e12d7d5084a86a03a4cedb8976943
Source dataset
uspto-grants-2010_08
Patent number
US07767831B2

Reaction notes

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