Synthesis of Progesterone

Structure of Progesterone

C21H30O2

Principal investigator	William S. Johnson
Publication year	1971
Synthesis type	Total
Number of steps	18 (3 parts)
References	J. Am. Chem. Soc. 1971, 93, 4332. J. Am. Chem. Soc. 1978, 100, 4268.

Part 1 of 3

intermediate structure

+

intermediate structure

n-BuLi

THF

-60 °C to RT, ON, 73%

intermediate structure

(CH2OH)2, TsOH, Hydroquinone

Dean-Stark

PhH

Reflux, 43 h, 71% (88% BRSM)

intermediate structure

NaI

MEK

80 °C, 40 min, 99%

See the Finkelstein Reaction

intermediate structure

Ph3P

PhH

80 °C, 11 h, 94%

intermediate structure

Report an error in this part

Part 2 of 3

intermediate structure

+

intermediate structure

NaOEt

EtOH

Reflux, 4.5 h

intermediate structure

KOH

Ethylene Glycol, EtOH, H2O, 2-Methoxyethanol

80 to 135 °C, 5 h

intermediate structure

TsOH

CH2Cl2, MeOH

Reflux, 20 h, 41% (3 steps)

See the Fischer-Speier Esterification

intermediate structure

Red-Al

PhH, THF

-70 °C, 6 h

intermediate structure

Special reagent

THF

-15 °C to RT, 2.5 h

See the Grignard Reaction

intermediate structure

MeC(OMe)3

Dean-Stark

EtCO2H

115 °C, 16 h, 50% (3 steps)

See the Johnson-Claisen Rearrangement

intermediate structure

Red-Al

PhH, THF

-70 °C, 6 h, 85%

intermediate structure

Report an error in this part

Part 3 of 3

intermediate structure

+

intermediate structure

PhLi

Et2O, THF

-70 to -30 °C, 10 min

See the Wittig Reaction

intermediate structure

HCl

H2O, MeOH

40 °C, 6 h

intermediate structure

NaOH

H2O, MeOH

Reflux, 18 h, 46% (3 steps)

See the Aldol Condensation

intermediate structure

MeLi

Et2O

RT, 2 min, 99%

intermediate structure

Ethylene carbonate, CF3CO2H

DCE

0 °C, 3 h, 71%

"The product is a 83:17 mixture of diastereomers at C-17 (major shown)"

intermediate structure

O3
AcOH , Zn

CH2Cl2, MeOH

-70 to -15 °C, 32 min, 88%

intermediate structure

KOH

H2O, MeOH

RT, 20 h, 72%

See the Aldol Condensation

intermediate structure

Report an error in this part