Synthesis of Cholesterol

Structure of Cholesterol

C27H46O

Principal investigator	Robert B. Woodward
Publication year	1951
Synthesis type	Formal
Number of steps	35 (linear)
References	J. Am. Chem. Soc. 1951, 73, 2403. J. Am. Chem. Soc. 1951, 73, 3547. J. Am. Chem. Soc. 1951, 73, 3548. J. Am. Chem. Soc. 1952, 74, 4223.

Part 1 of 1

intermediate structure

1,3-Butadiene

PhH

100 °C, 96 h, 86%

See the Diels-Alder Reaction

intermediate structure

NaOH

Dioxane , H2O

40-50 °C, 90%

intermediate structure

LiAlH4

THF

Reflux, 65 min, 64%

intermediate structure

H2SO4

Dioxane , H2O

RT, 24 h, 99%

intermediate structure

Ac2O

Pyr

RT, 12 h, 96%

intermediate structure

Zn

Ac2O

Reflux, 8 min, 63%

intermediate structure

HCO2Et, NaOMe

PhH

RT, 30 min, 94%

See the Claisen Condensation

intermediate structure

KOt-Bu, NaOH, Ethyl vinyl ketone

H2O, t-BuOH

0 °C to RT, 10 h, 53%

See the Michael Addition

intermediate structure

KOH

Dioxane , H2O

0 °C, 3 h, 88%

intermediate structure

OsO4

Et2O

0 °C, 5-8 d, 57%

"A single, uncharacterized isomer was isolated."

intermediate structure

CuSO4

Acetone

RT, 36 h, 83%

intermediate structure

Pd/SrCO3, H2

1 atm

PhH

RT, 3.5 h, 85%

intermediate structure

HCO2Et, NaOMe

PhH

RT, ON

See the Claisen Condensation

intermediate structure

PhNHMe

MeOH

RT, 24 h, 88% (2 steps)

intermediate structure

VinylCN, Me3N+Bn HO-

H2O, PhH, t-BuOH

50 °C, 45 h

See the Michael Addition

intermediate structure

KOH

H2O

Reflux, 46% (2 steps)

"Also isolated was the C1-epimer (33 % yield)."

intermediate structure

NaOAc

Ac2O

Reflux, 2 h, 28%

intermediate structure

MeMgBr

Et2O, PhH

-18 °C, 3 h

See the Grignard Reaction

intermediate structure

NaOH

H2O, MeOH

Reflux, 2 h, 58% (2 steps)

See the Aldol Condensation

intermediate structure

HIO4

Dioxane , H2O

0 °C, 14 h

intermediate structure

Piperidine, AcOH

Dean-Stark

PhH

60 °C, 60 min, 66% (2 steps)

See the Aldol Condensation

intermediate structure

Na2Cr2O7

AcOH, H2O

RT, 10 h

intermediate structure

CH2N2

Et2O, PhH

RT, 20 min, 30% (2 steps)

intermediate structure

H2, PtO2

1 atm

AcOH

RT

intermediate structure

CrO3

AcOH

RT, ON, 2.4% (2 steps)

intermediate structure

NaBH4

EtOH

RT, 4 h, 64%

intermediate structure

KOH

H2O, MeOH

Reflux, 12 h, 100%

intermediate structure

Ac2O

Pyr

60 °C, 3 h, 92%

intermediate structure

SOCl2

0 °C to RT, 15.5 h, 90%

intermediate structure

MeCd

PhH

Reflux, 90 min, 92%

intermediate structure

+

intermediate structure

Et2O, PhH

RT, 60 min

See the Grignard Reaction

intermediate structure

Ac2O

AcOH

Reflux, 2.5 h

intermediate structure

PtO2, H2

AcOH

RT, 30 min, 14% (3 steps)

intermediate structure

KOH

H2O, MeOH

Reflux, 2 h, 85%

intermediate structure

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Remaining...

(5 steps)

"See : Org. Synth. 1937, 17, 43; Ber. 1935, 68, 2091; Helv. Chim. Acta 1938, 21, 866; J. Chem. Soc. 1950, 2325."

intermediate structure