Hydrochloric Acid → 2-((1-(Trityloxy)but-3-en-2-yl)oxy)acetaldehyde

HRID 707702Notes

Reaction equation

HRID 707702 reaction equation
[C:1]([O:20][CH2:21][CH:22]([O:25][CH2:26][C:27](OC(C)(C)C)=[O:28])[CH:23]=[CH2:24])([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.CC(C[AlH]CC(C)C)C.Cl>C(Cl)Cl>[C:1]([O:20][CH2:21][CH:22]([O:25][CH2:26][CH:27]=[O:28])[CH:23]=[CH2:24])([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

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14487Diisobutylaluminum hydrideHCID 70557162Tert-butyl 2-((1-(trityloxy)but-3-en-2-yl)oxy)acetate

Product 1

HCID 867244052-((1-(Trityloxy)but-3-en-2-yl)oxy)acetaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Crude mixture from Step 4-(3) (tert-butyl 2-((1-(trityloxy)but-3-en-2-yl)oxy)acetate 3.01 kg, 6.771 mol, 1.00 equiv.) was dissolved in CH2Cl2 (5.81 L). The reaction mixture was cooled down to −78° C. DIBAL (1.5 M in toluene, 4.14 L, 6.19 mol, 1.00 equiv.) was added in portions while maintaining temperature below −65° C. The reaction was stirred at −78° C. for additional 30 min. Aq. HCl (4.00 L, 2.0 M) was added slowly to the reaction mixture while maintaining temperature below −60° C. The reaction was then warmed up to 16.8° C. Aq. HCl (2.0 M, 3.50 L) was added slowly to the reaction mixture. The organic phase was extracted then successively washed with aq. HCl (1M, 7.50 L) and 10% aq.NaHCO3 (3.75 L). The organic phase was was taken to the next step as a crude solution (11.48 kg). 1H NMR (500 MHz, DMSO) δ ppm 9.62 (s, 1H), 7.43 (dd, J=8.3, 0.9 Hz, 6H), 7.32 (dd, J=13.5, 5.6 Hz, 6H), 7.25 (t, J=7.3 Hz, 3H), 5.81-5.70 (m, 1H), 5.30 (dd, J=17.3, 1.0 Hz, 1H), 5.24 (dd, J=10.4, 0.8 Hz, 1H), 4.19 (q, J=18.2 Hz, 2H), 4.05 (dd, J=11.4, 6.2 Hz, 1H), 3.16 (dd, J=9.7, 6.3 Hz, 1H), 3.05 (dd, J=9.7, 4.4 Hz, 1H); 13C NMR (125 MHz, DMSO) δ ppm 201.70, 144.14, 135.92, 128.75, 128.32, 127.48, 119.01, 86.55, 80.79, 74.60, 66.57.

Workup

  1. temperaturewhile maintaining temperature below −65° C
  2. temperaturewhile maintaining temperature below −60° C
  3. temperatureThe reaction was then warmed up to 16.8° C
  4. extractionThe organic phase was extracted
  5. washthen successively washed with aq. HCl (1M, 7.50 L) and 10% aq

Sources & evidence

ORD record
ord-4d4ba060882542c59361f1e57586fd81
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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