Diisobutylaluminumhydride → [(4S)-4-(tritylamino)cyclopent-1-en-1-yl]methanol

HRID 1427331Notes

Reaction equation

HRID 1427331 reaction equation
[C:1]([NH:20][C@@H:21]1[CH2:25][C:24]([C:26](OC)=[O:27])=[CH:23][CH2:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[C:1]([NH:20][C@@H:21]1[CH2:25][C:24]([CH2:26][OH:27])=[CH:23][CH2:22]1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 86627068Methyl (4S)-4-(tritylamino)cyclopent-1-ene-1-carboxylate

Product 1

HCID 68636580[(4S)-4-(tritylamino)cyclopent-1-en-1-yl]methanolYield 116.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-7.5 °C

Procedure

A reactor was charged with methyl (4S)-4-(tritylamino)cyclopent-1-ene-1-carboxylate (4.75 kg, 12.4 mol). The reactor was charged with anhydrous toluene (9.5 L), cooled to −5 to −10° C. and the agitation started. While maintaining the temperature between −10° C. and +10° C., diisobutylaluminum hydride (1M solution in toluene, 23.4 kg, 27.3 mol) was added. Upon completion of the addition, the reaction mixture was analyzed by HPLC, which confirmed a complete conversion of the starting material to the product. The reaction mixture was quenched into cold 2 N NaOH solution (−5 to −10° C.) at a rate to keep the internal temperature below 20° C. The organic phase was separated and filtered through a pad of diatomaceous earth. The pad was washed with toluene (2×1 L), and the filtrate was concentrated under reduced pressure to afford the title compound as a thick oil (5.15 kg). The product was diluted with methylene chloride and stored as a solution at 0 to 5° C. 1H NMR (300 MHz, CDCl3, δ): 7.60-7.56 (m, 5H), 7.35-7.17 (m, 10H), 5.38 (bs, 1H), 4.03-4.02 (d, J=3.7 Hz, 2H), 3.49-3.36 (m, 1H), 2.40 (s, 2H), 2.19-1.79 (m, 4H), 1.32-1.29 (t, J=5.8 Hz, 1H).

Workup

  1. additionwas added
  2. additionUpon completion of the addition
  3. customThe reaction mixture was quenched into cold 2 N NaOH solution (−5 to −10° C.) at a rate
  4. customthe internal temperature below 20° C
  5. customThe organic phase was separated
  6. filtrationfiltered through a pad of diatomaceous earth
  7. washThe pad was washed with toluene (2×1 L)
  8. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-02fa796fd00849a499f0f4cacaf82fe7
Source dataset
uspto-grants-2015_01
Patent number
US08933225B2

Reaction notes

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